The extracellular matrix (ECM)-and its mechanobiology-regulates key cellular functions that drive tumor growth and development. Accordingly, mechanotherapy is emerging as an effective approach to treat fibrotic diseases such as cancer. Through restoring the ECM to healthy-like conditions, this treatment aims to improve tissue perfusion, facilitating the delivery of chemotherapies. In particular, the manipulation of ECM is gaining interest as a valuable strategy for developing innovative treatments based on nanoparticles (NPs). However, further progress is required; for instance, it is known that the presence of a dense ECM, which hampers the penetration of NPs, primarily impacts the efficacy of nanomedicines. Furthermore, most 2D in vitro studies fail to recapitulate the physiological deposition of matrix components. To address these issues, a comprehensive understanding of the interactions between the ECM and NPs is needed. This review focuses on the main features of the ECM and its complex interplay with NPs. Recent advances in mechanotherapy are discussed and insights are offered into how its combination with nanomedicine can help improve nanomaterials design and advance their clinical translation.

Department of Chemical Engineering The University of Melbourne Parkville Victoria 3010 Australia

Dipartimento di Scienze e Tecnologie Chimiche Universita di Roma Tor Vergata Via della Ricerca Scientifica 1 Rome 00133 Italy

International Clinical Research Center St Anne's University Hospital Brno 60200 Czech Republic

School of Cardiovascular and Metabolic Medicine and Sciences King's College London London WC2R 2LS UK

School of Science RMIT University Melbourne Victoria 3000 Australia

Zobrazit více v PubMed

Pickup M. W., Mouw J. K., Weaver V. M., EMBO Rep. 2014, 15, 1243. PubMed PMC

Frantz C., Stewart K. M., Weaver V. M., J. Cell Sci. 2010, 123, 4195. PubMed PMC

Winkler J., Abisoye‐Ogunniyan A., Metcalf K. J., Werb Z., Nat. Commun. 2020, 11, 5120. PubMed PMC

Reuten R., Zendehroud S., Nicolau M., Fleischhauer L., Laitala A., Kiderlen S., Nikodemus D., Wullkopf L., Nielsen S. R., McNeilly S., Prein C., Rafaeva M., Schoof E. M., Furtwängler B., Porse B. T., Kim H., Won K. J., Sudhop S., Zornhagen K. W., Suhr F., Maniati E., Pearce O. M. T., Koch M., Oddershede L. B., Van Agtmael T., Madsen C. D., Mayorca‐Guiliani A. E., Bloch W., Netz R. R., Clausen‐Schaumann H., et al., Nat. Mater. 2021, 20, 892. PubMed

Lamandé S. R., Bateman J. F., Anat Rec (Hoboken) 2020, 303, 1527. PubMed PMC

Bateman J. F., Boot‐Handford R. P., Lamandé S. R., Nat. Rev. Genet. 2009, 10, 173. PubMed

Robinson P. N., Arteaga‐Solis E., Baldock C., Collod‐Béroud G., Booms P., De Paepe A., Dietz H. C., Guo G., Handford P. A., Judge D. P., Kielty C. M., Loeys B., Milewicz D. M., Ney A., Ramirez F., Reinhardt D. P., Tiedemann K., Whiteman P., Godfrey M., J Med Genet 2006, 43, 769. PubMed PMC

Colige A., Nuytinck L., Hausser I., van Essen A. J., Thiry M., Herens C., Adès L. C., Malfait F., Paepe A. D., Franck P., Wolff G., Oosterwijk J. C., Smitt J. H., Lapière C. M., Nusgens B. V., J. Invest. Dermatol. 2004, 123, 656. PubMed

Byers P. H., Murray M. L., Matrix Biol. 2014, 33, 10. PubMed

Millington‐Ward S., McMahon H. P., Farrar G. J., Trends Mol. Med. 2005, 11, 299. PubMed

Sleeboom J. J. F., van Tienderen G. S., Schenke‐Layland K., van der Laan L. J. W., Khalil A. A., Verstegen M. M. A., Sci. Transl. Med. 2024, 16, eadg3840. PubMed

Cox T. R., Nat. Rev. Cancer 2021, 21, 217. PubMed

Sahai E., Astsaturov I., Cukierman E., DeNardo D. G., Egeblad M., Evans R. M., Fearon D., Greten F. R., Hingorani S. R., Hunter T., Hynes R. O., Jain R. K., Janowitz T., Jorgensen C., Kimmelman A. C., Kolonin M. G., Maki R. G., Powers R. S., Puré E., Ramirez D. C., Scherz‐Shouval R., Sherman M. H., Stewart S., Tlsty T. D., Tuveson D. A., Watt F. M., Weaver V., Weeraratna A. T., Werb Z., Nature Reviews. Cancer 2020, 20, 174. PubMed PMC

Liu T., Han C., Wang S., Fang P., Ma Z., Xu L., Yin R., J. Hematol. Oncol. 2019, 12, 86. PubMed PMC

Sheridan C., Nat. Biotechnol. 2019, 37, 829. PubMed

a) Jain R. K., Stylianopoulos T., Nature Reviews. Clinical Oncology 2010, 7, 653; PubMed PMC

b) Netti P. A., Berk D. A., Swartz M. A., Grodzinsky A. J., Jain R. K., Cancer Res. 2000, 60, 2497; PubMed

c) Zhao Y., Zheng X., Zheng Y., Chen Y., Fei W., Wang F., Zheng C., Front. Oncol. 2021, 11, 650453; PubMed PMC

d) Villegas M. R., Baeza A., Vallet‐Regí M., ACS Appl. Mater. Interfaces 2015, 7, 24075. PubMed

Vargason A. M., Anselmo A. C., Mitragotri S., Nat. Biomed. Eng. 2021, 5, 951. PubMed

Ikenaga N., Peng Z. W., Vaid K. A., Liu S. B., Yoshida S., Sverdlov D. Y., Mikels‐Vigdal A., Smith V., Schuppan D., Popov Y. V., Gut 2017, 66, 1697. PubMed PMC

Wen B., Xu L.‐Y., Li E.‐M., Biochimica et Biophysica Acta (BBA) – Reviews on Cancer 2020, 1874, 188435. PubMed

a) Raghu G., Brown K. K., Collard H. R., Cottin V., Gibson K. F., Kaner R. J., Lederer D. J., Martinez F. J., Noble P. W., Song J. W., Wells A. U., Whelan T. P., Wuyts W., Moreau E., Patterson S. D., Smith V., Bayly S., Chien J. W., Gong Q., Zhang J. J., O'Riordan T. G., The Lancet. Respiratory Medicine 2017, 5, 22; PubMed

b) Hecht J. R., A. B. Benson 3rd, Vyushkov D., Yang Y., Bendell J., Verma U., The Oncologist 2017, 22, 243; PubMed PMC

c) A. B. Benson 3rd, Wainberg Z. A., Hecht J. R., Vyushkov D., Dong H., Bendell J., Kudrik F., The Oncologist 2017, 22, 241. PubMed PMC

Richeldi L., Fernández Pérez E. R., Costabel U., Albera C., Lederer D. J., Flaherty K. R., Ettinger N., Perez R., Scholand M. B., Goldin J., Peony Yu K. H., Neff T., Porter S., Zhong M., Gorina E., Kouchakji E., Raghu G., The Lancet. Respiratory medicine 2020, 8, 25. PubMed

Chen Q., Liu G., Liu S., Su H., Wang Y., Li J., Luo C., Trends Pharmacol. Sci. 2018, 39, 59. PubMed

Hua S., de Matos M. B. C., Metselaar J. M., Storm G., 2018, 9. PubMed PMC

van der Meel R., Lammers T., Hennink W. E., Expert Opinion on Drug Delivery 2017, 14, 1. PubMed PMC

a) Zhang D., Wang G., Yu X., Wei T., Farbiak L., Johnson L. T., Taylor A. M., Xu J., Hong Y., Zhu H., Siegwart D. J., Nat. Nanotechnol. 2022, 17, 777; PubMed PMC

b) Cassani M., Fernandes S., Oliver‐De La Cruz J., Durikova H., Vrbsky J., Patočka M., Hegrova V., Klimovic S., Pribyl J., Debellis D., Skladal P., Cavalieri F., Caruso F., Forte G., Adv. Sci. 2024, 11, 2302965. PubMed PMC

Hayward M.‐K., Muncie J. M., Weaver V. M., Dev. Cell 2021, 56, 1833. PubMed PMC

a) Butcher D. T., Alliston T., Weaver V. M., Nat. Rev. Cancer 2009, 9, 108; PubMed PMC

b) Hall M. S., Alisafaei F., Ban E., Feng X., Hui C.‐Y., Shenoy V. B., Wu M., Proc. Natl. Acad. Sci. USA 2016, 113, 14043; PubMed PMC

c) Radman B. A., Alhameed A. M. M., Shu G., Yin G., Wang M., J. Mater. Chem. B 2024, 12, 5299. PubMed

Cox T. R., Erler J. T., Dis Model Mech 2011, 4, 165. PubMed PMC

Yu H., Mouw J. K., Weaver V. M., Trends Cell Biol. 2011, 21, 47. PubMed PMC

a) Coban B., Bergonzini C., Zweemer A. J. M., Danen E. H. J., Br. J. Cancer 2021, 124, 49; PubMed PMC

b) Romani P., Valcarcel‐Jimenez L., Frezza C., Dupont S., Nat. Rev. Mol. Cell Biol. 2021, 22, 22. PubMed

Huang J., Zhang L., Wan D., Zhou L., Zheng S., Lin S., Qiao Y., Signal Transduction Targeted Ther. 2021, 6, 153. PubMed PMC

Papanicolaou M., Parker A. L., Yam M., Filipe E. C., Wu S. Z., Chitty J. L., Wyllie K., Tran E., Mok E., Nadalini A., Skhinas J. N., Lucas M. C., Herrmann D., Nobis M., Pereira B. A., Law A. M. K., Castillo L., Murphy K. J., Zaratzian A., Hastings J. F., Croucher D. R., Lim E., Oliver B. G., Mora F. V., Parker B. L., Gallego‐Ortega D., Swarbrick A., O'Toole S., Timpson P., Cox T. R., Nat. Commun. 2022, 13, 4587. PubMed PMC

Yuan Z., Li Y., Zhang S., Wang X., Dou H., Yu X., Zhang Z., Yang S., Xiao M., Mol Cancer 2023, 22, 48. PubMed PMC

Panciera T., Citron A., Di Biagio D., Battilana G., Gandin A., Giulitti S., Forcato M., Bicciato S., Panzetta V., Fusco S., Azzolin L., Totaro A., Dei Tos A. P., Fassan M., Vindigni V., Bassetto F., Rosato A., Brusatin G., Cordenonsi M., Piccolo S., Nat. Mater. 2020, 19, 797. PubMed PMC

Kai F., Drain A. P., Weaver V. M., Dev. Cell 2019, 49, 332. PubMed PMC

Chiang S. P., Cabrera R. M., Segall J. E., Am. J. Physiol. Cell Physiol. 2016, 311, C1. PubMed PMC

Yankaskas C. L., Bera K., Stoletov K., Serra S. A., Carrillo‐Garcia J., Tuntithavornwat S., Mistriotis P., Lewis J. D., Valverde M. A., Konstantopoulos K., Sci. Adv. 2021, 7. PubMed PMC

Henke E., Nandigama R., Ergün S., Front. Mol. Biosci. 2019, 6, 160. PubMed PMC

Salmon H., Donnadieu E., Oncoimmunology 2012, 1, 992. PubMed PMC

Barbier A. J., Jiang A. Y., Zhang P., Wooster R., Anderson D. G., Nat. Biotechnol. 2022, 40, 840. PubMed

Fernandes S., Cassani M., Cavalieri F., Forte G., Caruso F., Adv. Sci. (Weinh) 2024, 11, e2305769. PubMed PMC

Mohammadi H., Sahai E., Nat. Cell Biol. 2018, 20, 766. PubMed

Calvo F., Ege N., Grande‐Garcia A., Hooper S., Jenkins R. P., Chaudhry S. I., Harrington K., Williamson P., Moeendarbary E., Charras G., Sahai E., Nat. Cell Biol. 2013, 15, 637. PubMed PMC

Nardone G., Oliver‐De La Cruz J., Vrbsky J., Martini C., Pribyl J., Skládal P., Pešl M., Caluori G., Pagliari S., Martino F., Maceckova Z., Hajduch M., Sanz‐Garcia A., Pugno N. M., Stokin G. B., Forte G., Nat. Commun. 2017, 8, 15321. PubMed PMC

Pan Z., Tian Y., Cao C., Niu G., Mol. Cancer Res. 2019, 17, 1777. PubMed

Nguyen C. D. K., Yi C., Trends Cancer 2019, 5, 283. PubMed PMC

Seong J., Wang N., Wang Y., 2013, 17, 597. PubMed PMC

Mitra S. K., Hanson D. A., Schlaepfer D. D., Nat. Rev. Mol. Cell Biol. 2005, 6, 56. PubMed

a) Kim N.‐G., Gumbiner B. M., J. Cell Biol. 2015, 210, 503; PubMed PMC

b) Dupont S., Morsut L., Aragona M., Enzo E., Giulitti S., Cordenonsi M., Zanconato F., Le Digabel J., Forcato M., Bicciato S., Elvassore N., Piccolo S., Nature 2011, 474, 179; PubMed

c) Moroishi T., Hansen C. G., Guan K. L., Nature reviews. Cancer 2015, 15, 73. PubMed PMC

Oliver‐De La Cruz J., Nardone G., Vrbsky J., Pompeiano A., Perestrelo A. R., Capradossi F., Melajová K., Filipensky P., Forte G., Biomaterials 2019, 205, 64. PubMed

a) Kalli M., Poskus M. D., Stylianopoulos T., Zervantonakis I. K., Trends Cancer 2023, 9, 937; PubMed PMC

b) Coste B., Murthy S. E., Mathur J., Schmidt M., Mechioukhi Y., Delmas P., Patapoutian A., Nat. Commun. 2015, 6, 7223. PubMed PMC

Syeda R., Florendo M. N., Cox C. D., Kefauver J. M., Santos J. S., Martinac B., Patapoutian A., Cell Rep. 2016, 17, 1739. PubMed PMC

Yu J.‐L., Liao H.‐Y., Biomed. Pharmacother. 2021, 140, 111692. PubMed

Dasgupta I., McCollum D., J. Biol. Chem. 2019, 294, 17693. PubMed PMC

Derynck R., Turley S. J., Akhurst R. J., Nat. Rev. Clin. Oncol. 2021, 18, 9. PubMed PMC

Mariathasan S., Turley S. J., Nickles D., Castiglioni A., Yuen K., Wang Y., Kadel Iii E. E., Koeppen H., Astarita J. L., Cubas R., Jhunjhunwala S., Banchereau R., Yang Y., Guan Y., Chalouni C., Ziai J., Şenbabaoğlu Y., Santoro S., Sheinson D., Hung J., Giltnane J. M., Pierce A. A., Mesh K., Lianoglou S., Riegler J., Carano R. A. D., Eriksson P., Höglund M., Somarriba L., Halligan D. L., et al., Nature 2018, 554, 544. PubMed PMC

Massagué J., Cell 2008, 134, 215; PubMed

Fernandes S., Oliver‐De La Cruz J., Morazzo S., Niro F., Cassani M., Ďuríková H., Caravella A., Fiore P., Azzato G., De Marco G., Lauria A., Izzi V., Bosáková V., Fric J., Filipensky P., Forte G., Matrix Biology: Journal of the International Society for Matrix Biology 2024, 125, 12. PubMed

Wilhelm S., Tavares A. J., Dai Q., Ohta S., Audet J., Dvorak H. F., Chan W. C. W., Nat. Rev. Mater. 2016, 1, 16014.

Ouyang B., Poon W., Zhang Y.‐N., Lin Z. P., Kingston B. R., Tavares A. J., Zhang Y., Chen J., Valic M. S., Syed A. M., MacMillan P., Couture‐Senécal J., Zheng G., Chan W. C. W., Nat. Mater. 2020, 19, 1362. PubMed

Tian Y., Cheng T., Sun F., Zhou Y., Yuan C., Guo Z., Wang Z., Adv. Colloid Interface Sci. 2024, 326, 103124. PubMed

a) Li M., Zhang Y., Zhang Q., Li J., Mater. Today Bio. 16, 100364; PubMed PMC

b) Xu X., Wu Y., Qian X., Wang Y., Wang J., Li J., Li Y., Zhang Z., Adv. Healthcare Mater. 2022, 11, e2101428. PubMed

a) Smith L. R., Cho S., Discher D. E., Physiology (Bethesda) 2018, 33, 16; PubMed PMC

b) Zhang X., Zhang S., Wang T., Stem Cell Research & Therapy 2022, 13, 415. PubMed PMC

De Belly H., Stubb A., Yanagida A., Labouesse C., Jones P. H., Paluch E. K., Chalut K. J., Cell Stem Cell 2021, 28, 273. PubMed PMC

Heldin C.‐H., Rubin K., Pietras K., Östman A., Nat. Rev. Cancer 2004, 4, 806. PubMed

Stylianopoulos T., Poh M. Z., Insin N., Bawendi M. G., Fukumura D., Munn L. L., Jain R. K., Biophys. J. 2010, 99, 1342. PubMed PMC

a) Zhang S., Moustafa Y., Huo Q., ACS Appl. Mater. Interfaces 2014, 6, 21184; PubMed

b) Walters R., Medintz I. L., Delehanty J. B., Stewart M. H., Susumu K., Huston A. L., Dawson P. E., Dawson G., ASN neuro. 2015, 7, 10.1177/1759091415592389 PubMed DOI PMC

Bandara S. R., Molley T. G., Kim H., Bharath P. A., Kilian K. A., Leal C., Mater. Horiz. 2020, 7, 125. PubMed PMC

a) Agarwal R., Jurney P., Raythatha M., Singh V., Sreenivasan S. V., Shi L., Roy K., Adv. Healthcare Mater. 2015, 4, 2269; PubMed PMC

b) Le Goas M., Testard F., Taché O., Debou N., Cambien B., Carrot G., Renault J.‐P., Langmuir 2020, 36, 10460. PubMed

Chauhan V. P., Popović Z., Chen O., Cui J., Fukumura D., Bawendi M. G., Jain R. K., Angewandte Chemie (International ed. in English) 2011, 50, 11417. PubMed PMC

a) Jiang T., Zhang B., Shen S., Tuo Y., Luo Z., Hu Y., Pang Z., Jiang X., ACS Appl. Mater. Interfaces 2017, 9, 31497; PubMed

b) Xu F., Huang X., Wang Y., Zhou S., Adv. Mater. 2020, 32, 1906745. PubMed

a) Yao H., Guo X., Zhou H., Ren J., Li Y., Duan S., Gong X., Du B., ACS Appl. Mater. Interfaces 2020, 12, 20214; PubMed

b) Wang X., Luo J., He L., Cheng X., Yan G., Wang J., Tang R., J. Colloid Interface Sci. 2018, 525, 269; PubMed

c) Li H. J., Du J. Z., Du X. J., Xu C. F., Sun C. Y., Wang H. X., Cao Z. T., Yang X. Z., Zhu Y. H., Nie S., Wang J., Proc. Natl. Acad. Sci. USA 2016, 113, 4164. PubMed PMC

a) Ruan S., Cao X., Cun X., Hu G., Zhou Y., Zhang Y., Lu L., He Q., Gao H., Biomaterials 2015, 60, 100; PubMed

b) Wong C., Stylianopoulos T., Cui J., Martin J., Chauhan V. P., Jiang W., Popović Z., Jain R. K., Bawendi M. G., Fukumura D., 2011, 108, 2426. PubMed PMC

Reddy B. D., Beeraka N. M., Chitturi C. M. K., Madhunapantula S. V., Curr. Pharm. Des. 2021, 27, 3337. PubMed

Wang J., Wang Y., Cao H., Wang H., Li J., Li Y., Li Y., Zhang Z., J. Controlled Release 2020, 323, 59. PubMed

Engin A. B., Nikitovic D., Neagu M., Henrich‐Noack P., Docea A. O., Shtilman M. I., Golokhvast K., Tsatsakis A. M., Part. Fibre Toxicol. 2017, 14, 22. PubMed PMC

a) Raeesi V., Chan W. C. W., Nanoscale 2016, 8, 12524; PubMed

b) Huo S., Ma H., Huang K., Liu J., Wei T., Jin S., Zhang J., He S., Liang X.‐J., Cancer Res. 2013, 73, 319. PubMed

a) Cabral H., Matsumoto Y., Mizuno K., Chen Q., Murakami M., Kimura M., Terada Y., Kano M. R., Miyazono K., Uesaka M., Nishiyama N., Kataoka K., Nat. Nanotechnol. 2011, 6, 815; PubMed

b) Goodman T. T., Olive P. L., Pun S. H., Int. J. Nanomed. 2007, 2, 265. PubMed PMC

a) Ataide J. A., Gérios E. F., Mazzola P. G., Souto E. B., Adv. Colloid Interface Sci. 2018, 254, 48; PubMed

b) Wu D., Chen X., Zhou J., Chen Y., Wan T., Wang Y., Lin A., Ruan Y., Chen Z., Song X., Fang W., Duan H., Ping Y., Mater. Horiz. 2020, 7, 2929.

a) Jung H. S., Verwilst P., Sharma A., Shin J., Sessler J. L., Kim J. S., Chem. Soc. Rev. 2018, 47, 2280; PubMed PMC

b) Lo P.‐C., Rodríguez‐Morgade M. S., Pandey R. K., Ng D. K. P., Torres T., Dumoulin F., Chem. Soc. Rev. 2020, 49, 1041; PubMed

c) Lee S., Han H., Koo H., Na J. H., Yoon H. Y., Lee K. E., Lee H., Kim H., Kwon I. C., Kim K., Journal of Controlled Release: Official Journal of The Controlled Release Society 2017, 263, 68; PubMed

d) Kolosnjaj‐Tabi J., Marangon I., Nicolas‐Boluda A., Silva A. K. A., Gazeau F., Pharmacological Research 2017, 126, 123; PubMed

e) Zhang D., Feng F., Li Q., Wang X., Yao L., Biomaterials 2018, 173, 22; PubMed

f) You D. G., Yoon H. Y., Jeon S., Um W., Son S., Park J. H., Kwon I. C., Kim K., Nano Convergence 2017, 4, 30. PubMed PMC

Piehler S., Wucherpfennig L., Tansi F. L., Berndt A., Quaas R., Teichgraeber U., Hilger I., Nanomedicine: Nanotechnology, Biology, and Medicine 2020, 28, 102183. PubMed

a) Tansi F. L., Fröbel F., Maduabuchi W. O., Steiniger F., Westermann M., Quaas R., Teichgräber U. K., Hilger I., Nanomaterials (Basel, Switzerland) 2021, 11, 438; PubMed PMC

b) Gong H., Chao Y., Xiang J., Han X., Song G., Feng L., Liu J., Yang G., Chen Q., Liu Z., Nano Lett. 2016, 16, 2512; PubMed

c) Li J., Xie C., Huang J., Jiang Y., Miao Q., Pu K., 2018, 57, 3995. PubMed

DuFort C. C., DelGiorno K. E., Carlson M. A., Osgood R. J., Zhao C., Huang Z., Thompson C. B., Connor R. J., Thanos C. D., Scott Brockenbrough J., Provenzano P. P., Frost G. I., Michael Shepard H., Hingorani S. R., Biophys. J. 2016, 110, 2106. PubMed PMC

Lan H.‐R., Lin F., Zhou Q., Huang L., Jin K., 2016.

a) Zhao H., Xu J., Wang Y., Sun C., Bao L., Zhao Y., Yang X., Zhao Y., ACS Nano 2022, 16, 3070; PubMed

b) Zhao H., Xu J., Feng C., Ren J., Bao L., Zhao Y., Tao W., Zhao Y., Yang X., Adv. Mater. 2022, 34, 2106390. PubMed

Fan Y., Du W., He B., Fu F., Yuan L., Wu H., Dai W., Zhang H., Wang X., Wang J., Zhang X., Zhang Q., Biomaterials 2013, 34, 2277. PubMed

Gao X., Zhang J., Huang Z., Zuo T., Lu Q., Wu G., Shen Q., ACS Appl. Mater. Interfaces 2017, 9, 29457. PubMed

a) Xie Y., Hang Y., Wang Y., Sleightholm R., Prajapati D. R., Bader J., Yu A., Tang W., Jaramillo L., Li J., Singh R. K., Oupický D., ACS Nano 2020, 14, 255; PubMed PMC

b) Fan J., Xu G., Chang Z., Zhu L., Yao J., Clinical science 2020, 134, 807. PubMed

Han X., Li Y., Xu Y., Zhao X., Zhang Y., Yang X., Wang Y., Zhao R., Anderson G. J., Zhao Y., Nie G., Nat. Commun. 2018, 9, 3390. PubMed PMC

a) Wang S.‐B., Chen Z.‐X., Gao F., Zhang C., Zou M.‐Z., Ye J.‐J., Zeng X., Zhang X.‐Z., Biomaterials 2020, 234, 119772; PubMed

b) Ji T., Lang J., Wang J., Cai R., Zhang Y., Qi F., Zhang L., Zhao X., Wu W., Hao J., Qin Z., Zhao Y., Nie G., ACS Nano 2017, 11, 8668. PubMed

Fang T., Zhang J., Zuo T., Wu G., Xu Y., Yang Y., Yang J., Shen Q., ACS Appl. Mater. Interfaces 2020, 12, 31292. PubMed

Chen Y., Song W., Shen L., Qiu N., Hu M., Liu Y., Liu Q., Huang L., ACS Nano 2019, 13, 1751. PubMed

a) Hou L., Chen D., Wang R., Wang R., Zhang H., Zhang Z., Nie Z., Lu S., Angew Chem Int Ed Engl 2021, 60, 6581; PubMed

b) Diop‐Frimpong B., Chauhan V. P., Krane S., Boucher Y., Jain R. K., Proc Natl Acad Sci 2011, 108, 2909. PubMed PMC

Hauge A., Rofstad E. K., Journal of Translational Medicine 2020, 18, 207. PubMed PMC

Murphy J. E., Wo J. Y., Ryan D. P., Clark J. W., Jiang W., Yeap B. Y., Drapek L. C., Ly L., Baglini C. V., Blaszkowsky L. S., Ferrone C. R., Parikh A. R., Weekes C. D., Nipp R. D., Kwak E. L., Allen J. N., Corcoran R. B., Ting D. T., Faris J. E., Zhu A. X., Goyal L., Berger D. L., Qadan M., Lillemoe K. D., Talele N., Jain R. K., DeLaney T. F., Duda D. G., Boucher Y., Fernández‐Del Castillo C., et al., JAMA oncology 2019, 5, 1020. PubMed PMC

Chauhan V. P., Martin J. D., Liu H., Lacorre D. A., Jain S. R., Kozin S. V., Stylianopoulos T., Mousa A. S., Han X., Adstamongkonkul P., Popović Z., Huang P., Bawendi M. G., Boucher Y., Jain R. K., Nat. Commun. 2013, 4, 2516. PubMed PMC

a) Cun X., Chen J., Li M., He X., Tang X., Guo R., Deng M., Li M., Zhang Z., He Q., ACS Appl. Mater. Interfaces 2019, 11, 39545; PubMed

b) Zhao J., Wang H., Hsiao C. H., Chow D. S., Koay E. J., Kang Y., Wen X., Huang Q., Ma Y., Bankson J. A., Ullrich S. E., Overwijk W., Maitra A., Piwnica‐Worms D., Fleming J. B., Li C., Biomaterials 2018, 159, 215. PubMed PMC

Golombek S. K., May J. N., Theek B., Appold L., Drude N., Kiessling F., Lammers T., Adv. Drug Delivery Rev. 2018, 130, 17. PubMed PMC

a) Danhier F., Journal of Controlled Release: Official Journal of the Controlled Release Society 2016, 244, 108; PubMed

b) Fernandes S., Cassani M., Pagliari S., Filipensky P., Cavalieri F., Forte G., Curr. Med. Chem. 2020, 27, 7234. PubMed

a) Zhou Q., Shao S., Wang J., Xu C., Xiang J., Piao Y., Zhou Z., Yu Q., Tang J., Liu X., Gan Z., Mo R., Gu Z., Shen Y., Nat. Nanotechnol. 2019, 14, 799; PubMed

b) Sindhwani S., Syed A. M., Ngai J., Kingston B. R., Maiorino L., Rothschild J., MacMillan P., Zhang Y., Rajesh N. U., Hoang T., Wu J. L. Y., Wilhelm S., Zilman A., Gadde S., Sulaiman A., Ouyang B., Lin Z., Wang L., Egeblad M., Chan W. C. W., Nat. Mater. 2020, 19, 566. PubMed

Kingston B. R., Lin Z. P., Ouyang B., MacMillan P., Ngai J., Syed A. M., Sindhwani S., Chan W. C. W., ACS Nano 2021, 15, 14080. PubMed

a) Zhao X., Yang X., Wang X., Zhao X., Zhang Y., Liu S., Anderson G. J., Kim S. J., Li Y., Nie G., ACS Nano 2021, 15, 14149; PubMed

b) Huang Y., Chen Y., Zhou S., Chen L., Wang J., Pei Y., Xu M., Feng J., Jiang T., Liang K., Liu S., Song Q., Jiang G., Gu X., Zhang Q., Gao X., Chen J., Nat. Commun. 2020, 11, 622. PubMed PMC

Sugimoto H., Mundel T. M., Kieran M. W., Kalluri R., Cancer Biol. Therapy 2006, 5, 1640. PubMed

Miao L., Newby J. M., Lin C. M., Zhang L., Xu F., Kim W. Y., Forest M. G., Lai S. K., Milowsky M. I., Wobker S. E., Huang L., ACS Nano 2016, 10, 9243. PubMed PMC

Miao L., Liu Q., Lin C. M., Luo C., Wang Y., Liu L., Yin W., Hu S., Kim W. Y., Huang L., Cancer Res. 2017, 77, 719. PubMed PMC

Zhou S., Zhen Z., Paschall A. V., Xue L., Yang X., Bebin‐Blackwell A. G., Cao Z., Zhang W., Wang M., Teng Y., Zhou G., Li Z., Avci F. Y., Tang W., Xie J., Adv. Funct. Mater. 2021, 31. PubMed PMC

Wang Z., Yang Q., Tan Y., Tang Y., Ye J., Yuan B., Yu W., Frontiers in cell and developmental biology 2021, 9, 613534. PubMed PMC

Wang L., Yang H., Dorn P., Berezowska S., Blank F., Wotzkow C., Marti T. M., Peng R.‐W., Harrer N., Sommergruber W., Kocher G. J., Schmid R. A., Hall S. R. R., eBioMedicine 2021, 73, 103664. PubMed PMC

Haber T., Cornejo Y. R., Aramburo S., Flores L., Cao P., Liu A., Mooney R., Gilchrist M., Tirughana R., Nwokafor U., Abidi W., Han E., Dellinger T., Wakabayashi M. T., Aboody K. S., Berlin J. M., Proc. Natl. Acad. Sci. USA 2020, 117, 19737. PubMed PMC

Miller M. A., Zheng Y.‐R., Gadde S., Pfirschke C., Zope H., Engblom C., Kohler R. H., Iwamoto Y., Yang K. S., Askevold B., Kolishetti N., Pittet M., Lippard S. J., Farokhzad O. C., Weissleder R., Nat. Commun. 2015, 6, 8692. PubMed PMC

Dai Q., Wilhelm S., Ding D., Syed A. M., Sindhwani S., Zhang Y., Chen Y. Y., MacMillan P., Chan W. C. W., ACS Nano 2018, 12, 8423. PubMed

a) Luo J., Gong T., Ma L., Carbohydr. Polym. 2020, 249, 116887; PubMed

b) Villegas M. R., Baeza A., Noureddine A., Durfee P. N., Butler K. S., Agola J. O., Brinker C. J., Vallet‐Regí M., Chem. Mater. 2018, 30, 112.

Wang H., Han X., Dong Z., Xu J., Wang J., Liu Z., 2019, 29, 1902440.

Wang Y., Gao Z., Du X., Chen S., Zhang W., Wang J., Li H., He X., Cao J., Wang J., Biomater. Sci. 2020, 8, 5121. PubMed

Wang S., Yang Y., Ma P., Zha Y., Zhang J., Lei A., Li N., eBioMedicine 2022, 76, 103873. PubMed PMC

a) Andón F. T., Digifico E., Maeda A., Erreni M., Mantovani A., Alonso M. J., Allavena P., Semin. Immunol. 2017, 34, 103; PubMed

b) He Y., de Araújo Júnior R. F., Cruz L. J., Eich C., Pharmaceutics 2021, 13, 1670. PubMed PMC

a) Nelson C. M., Bissell M. J., Annu. Rev. Cell Dev. Biol. 2006, 22, 287; PubMed PMC

b) Helmlinger G., Netti P. A., Lichtenbeld H. C., Melder R. J., Jain R. K., Nat. Biotechnol. 1997, 15, 778. PubMed

Rekad Z., Izzi V., Lamba R., Ciais D., Van Obberghen‐Schilling E., Matrix biology: journal of the International Society for Matrix Biology 2022, 111, 26. PubMed

Unal A. Z., West J. L., Bioconjugate Chem. 2020, 31, 2253. PubMed

Gilchrist A. E., Lee S., Hu Y., Harley B. A. C., 2019, 8, 1900751.

He W., Wang Q., Tian X., Pan G., Exploration 2022, 2, 20210093. PubMed PMC

Pozzi S., Scomparin A., Israeli Dangoor S., Rodriguez Ajamil D., Ofek P., Neufeld L., Krivitsky A., Vaskovich‐Koubi D., Kleiner R., Dey P., Koshrovski‐Michael S., Reisman N., Satchi‐Fainaro R., Adv. Drug Delivery Rev. 2021, 175, 113760. PubMed

Neufeld L., Yeini E., Pozzi S., Satchi‐Fainaro R., Nat. Rev. Cancer 2022, 22, 679. PubMed

Neufeld L., Yeini E., Reisman N., Shtilerman Y., Ben‐Shushan D., Pozzi S., Madi A., Tiram G., Eldar‐Boock A., Ferber S., Grossman R., Ram Z., Satchi‐Fainaro R., Sci. Adv. 2021, 7, eabi9119. PubMed PMC

Arends F., Nowald C., Pflieger K., Boettcher K., Zahler S., Lieleg O., PLoS One 2015, 10, e0118090. PubMed PMC

a) van Tienderen G. S., Rosmark O., Lieshout R., Willemse J., de Weijer F., Elowsson Rendin L., Westergren‐Thorsson G., Doukas M., Groot Koerkamp B., van Royen M. E., van der Laan L. J. W., Verstegen M. M. A., Acta Biomater. 2023, 158, 115; PubMed

b) Yi B., Xu Q., Liu W., Bioactive Materials 2022, 15, 82. PubMed PMC

Perestrelo A. R., Silva A. C., Cruz J. O.‐D. L., Martino F., Horváth V., Caluori G., Polanský O., Vinarský V., Azzato G., Marco G. d., Žampachová V., Skládal P., Pagliari S., Rainer A., Pinto‐do‐Ó P., Caravella A., Koci K., Nascimento D. S., Forte G., 2021, 128, 24. PubMed

Mayorca‐Guiliani A. E., Madsen C. D., Cox T. R., Horton E. R., Venning F. A., Erler J. T., Nat. Med. 2017, 23, 890. PubMed

Naba A., Pearce O. M. T., Del Rosario A., Ma D., Ding H., Rajeeve V., Cutillas P. R., Balkwill F. R., Hynes R. O., J. Proteome Res. 2017, 16, 3083. PubMed PMC

de Andrade Natal R., Adur J., Cesar C. L., Vassallo J., Surgical and Experimental Pathology 2021, 4, 7.

Kim S., Min S., Choi Y. S., Jo S.‐H., Jung J. H., Han K., Kim J., An S., Ji Y. W., Kim Y.‐G., Cho S.‐W., Nat. Commun. 2022, 13, 1692. PubMed PMC

a) Drost J., Clevers H., Nat. Rev. Cancer 2018, 18, 407; PubMed

b) Driehuis E., Kretzschmar K., Clevers H., Nat. Protoc. 2020, 15, 3380; PubMed

c) LeSavage B. L., Suhar R. A., Broguiere N., Lutolf M. P., Heilshorn S. C., Nat. Mater. 2022, 21, 143. PubMed

Veninga V., Voest E. E., Cancer Cell 2021, 39, 1190. PubMed

Guo P., Liu D., Subramanyam K., Wang B., Yang J., Huang J., Auguste D. T., Moses M. A., Nat. Commun. 2018, 9, 130. PubMed PMC

Hui Y., Yi X., Wibowo D., Yang G., Middelberg A. P. J., Gao H., Zhao C. X., Sci. Adv. 2020, 6, eaaz4316. PubMed PMC

Mitchell M. J., Billingsley M. M., Haley R. M., Wechsler M. E., Peppas N. A., Langer R., Nat. Rev. Drug Discovery 2021, 20, 101. PubMed PMC

Zhu G. H., Gray A. B. C., Patra H. K., Trends Pharmacol. Sci. 2022, 43, 709. PubMed

Zalba S., ten Hagen T. L. M., Burgui C., Garrido M. J., J. Controlled Release 2022, 351, 22. PubMed

Herdiana Y., Wathoni N., Shamsuddin S., Muchtaridi M., OpenNano 2022, 7, 100048.

a) Besford Q. A., Cavalieri F., Caruso F., Adv. Mater. 2020, 32, 1904625; PubMed

b) Radziwon A., Bhangu S. K., Fernandes S., Cortez‐Jugo C., De Rose R., Dyett B., Wojnilowicz M., Laznickova P., Fric J., Forte G., Caruso F., Cavalieri F., Nanoscale 2022, 14, 3452. PubMed

Gavilán H., Avugadda S. K., Fernández‐Cabada T., Soni N., Cassani M., Mai B. T., Chantrell R., Pellegrino T., Chem. Soc. Rev. 2021, 50, 11614. PubMed

Riley R. S., Day E. S., Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017, 9, e1449. PubMed PMC

Cheng Q., Wei T., Farbiak L., Johnson L. T., Dilliard S. A., Siegwart D. J., Nat. Nanotechnol. 2020, 15, 313. PubMed PMC

Dilliard S. A., Cheng Q., Siegwart D. J., Proc. Natl. Acad. Sci. USA 2021, 118, e2109256118. PubMed PMC

a) Monopoli M. P., Åberg C., Salvati A., Dawson K. A., Nat. Nanotechnol. 2012, 7, 779; PubMed

b) Salvati A., Pitek A. S., Monopoli M. P., Prapainop K., Bombelli F. B., Hristov D. R., Kelly P. M., Åberg C., Mahon E., Dawson K. A., Nat. Nanotechnol. 2013, 8, 137; PubMed

c) Francia V., Yang K., Deville S., Reker‐Smit C., Nelissen I., Salvati A., ACS Nano 2019, 13, 11107. PubMed PMC

Yokoi K., Kojic M., Milosevic M., Tanei T., Ferrari M., Ziemys A., Cancer Res. 2014, 74, 4239. PubMed PMC

Zhao H., Wang Y., Bao L., Chen C., Acc. Mater. Res. 2022, 3, 812.

Tomasetti L., Breunig M., Adv. Healthcare Mater. 2018, 7, 1700739. PubMed

a) Xu Z., Wang Y., Zhang L., Huang L., ACS Nano 2014, 8, 3636; PubMed PMC

b) Zuo Z. Q., Chen K. G., Yu X. Y., Zhao G., Shen S., Cao Z. T., Luo Y. L., Wang Y. C., Wang J., Biomaterials 2016, 82, 48. PubMed

Swartz M. A., Fleury M. E., Annu. Rev. Biomed. Eng. 2007, 9, 229. PubMed

a) Chang C., Werb Z., Trends Cell Biol. 2001, 11, S37; PubMed PMC

b) Stamenkovic I., Semin. Cancer Biol. 2000, 10, 415. PubMed

a) McGrail D. J., Kieu Q. M., Dawson M. R., J. Cell Sci. 2014, 127, 2621; PubMed PMC

b) Moroishi T., Hayashi T., Pan W.‐W., Fujita Y., Holt M. V., Qin J., Carson D. A., Guan K.‐L., Cell 2016, 167, 1525. PubMed PMC

Zhang L., Zhao D., Wang Y., Zhang W., Zhang J., Fan J., Zhan Q., Chen J., Mol. Carcinog. 2021, 60, 113. PubMed

Lan Y., Zhang D., Xu C., Hance K. W., Marelli B., Qi J., Yu H., Qin G., Sircar A., Hernández V. M., Jenkins M. H., Fontana R. E., Deshpande A., Locke G., Sabzevari H., Radvanyi L., Lo K.‐M., 2018, 10, eaan5488.

Slack R. J., Macdonald S. J. F., Roper J. A., Jenkins R. G., Hatley R. J. D., Nat. Rev. Drug Discovery 2022, 21, 60. PubMed PMC

Wang‐Gillam A., Lim K. H., McWilliams R., Suresh R., Lockhart A. C., Brown A., Breden M., Belle J. I., Herndon J., Bogner S. J., Pedersen K., Tan B., Boice N., Acharya A., Abdiannia M., Gao F., Yoon H. H., Zhu M., Trikalinos N. A., Ratner L., Aranha O., Hawkins W. G., Herzog B. H., DeNardo D. G., Clin. Cancer Res. 2022, 28, 5254. PubMed PMC

a) Diop‐Frimpong B., Chauhan V. P., Krane S., Boucher Y., Jain R. K., Proc. Natl. Acad. Sci. USA 2011, 108, 2909; PubMed PMC

b) Zhou Z., Yan Y., Zhang Q., Cheng Y., Biomater. Sci. 2020, 8, 1658. PubMed

a) Huang C., Butler P. J., Tong S., Muddana H. S., Bao G., Zhang S., Nano Lett. 2013, 13, 1611; PubMed

b) Wei Q., Huang C., Zhang Y., Zhao T., Zhao P., Butler P., Zhang S., Adv. Mater. 2018, 30, 1707464; PubMed

c) Fattahi P., Yeh Y.‐T., Zhao T., Younesi M., Huang C., Terrones M., Zheng S., Brown J. L., Huh D. D., Zhang S., Butler P. J., Adv. Mater. Interfaces 2023, 10, 2300137.

Voigt J. L., Timmer J., Pennarola F., Christian J., Meng N., Blumberg J. W., Schwarz U. S., Grimm D., Cavalcanti‐Adam E. A., Advanced functional materials 2024, 34, 2304674.

Lee A., Sousa de Almeida M., Milinkovic D., Septiadi D., Taladriz‐Blanco P., Loussert‐Fonta C., Balog S., Bazzoni A., Rothen‐Rutishauser B., Petri‐Fink A., Nanoscale 2022, 14, 15141. PubMed PMC

Halder G., Dupont S., Piccolo S., Nat. Rev. Mol. Cell Biol. 2012, 13, 591. PubMed

Athirasala A., Patel S., Menezes P. P., Kim J., Tahayeri A., Sahay G., Bertassoni L. E., Nanomedicine: Nanotechnology, Biology and Medicine 2022, 42, 102550. PubMed PMC

Cassani M., Niro F., Durikova H., Morazzo S., Pereira‐Sousa D., Fernandes S., Vrbsky J., Oliver‐De La Cruz J., Klimovic S., Pribyl J., Loja T., Skladal P., Caruso F., Forte G., bioRxiv 2024, 10.1101/2024.07.07.599665. DOI

Bhangu S. K., Fernandes S., Beretta G. L., Tinelli S., Cassani M., Radziwon A., Wojnilowicz M., Sarpaki S., Pilatis I., Zaffaroni N., Forte G., Caruso F., Ashokkumar M., Cavalieri F., Adv. Mater. 2022, 34, 2107964. PubMed

Kong X., Gao P., Wang J., Fang Y., Hwang K. C., J. Hematol. Oncol. 2023, 16, 74. PubMed PMC

Jiang J., Wang F., Huang W., Sun J., Ye Y., Ou J., Liu M., Gao J., Wang S., Fu D., Chen B., Liu L., Peng F., Tu Y., Exploration 2023, 3, 20220147. PubMed PMC

Yan M., Chen Q., Liu T., Li X., Pei P., Zhou L., Zhou S., Zhang R., Liang K., Dong J., Wei X., Wang J., Terasaki O., Chen P., Gu Z., Jiang L., Kong B., Nat. Commun. 2023, 14, 4628. PubMed PMC