Most cited article - PubMed ID 27940304
The structure of polymer carriers controls the efficacy of the experimental combination treatment of tumors with HPMA copolymer conjugates carrying doxorubicin and docetaxel
Persistent luminescence nanoparticles (PLNPs) are innovative nanomaterials highly useful for bioimaging applications. Indeed, due to their particular optical properties, i.e., the ability to store the excitation energy before slowly releasing it for a prolonged period of time, they allow in vivo imaging without auto-fluorescence and with a high target to background ratio. However, as for most nanoparticles (NPs), without any special surface coating, they are rapidly opsonized and captured by the liver after systemic injection into small animals. To overcome this issue and prolong nanoparticle circulation in the bloodstream, a new stealth strategy was developed by covering their surface with poly(N-2-hydroxypropyl)methacrylamide (pHPMA), a highly hydrophilic polymer widely used in nanomedicine. Preliminary in vivo imaging results demonstrated the possibility of pHPMA as an alternative strategy to cover ZnGa2O4:Cr NPs to delay their capture by the liver, thereby providing a new perspective for the formulation of stealth NPs.
- Keywords
- HPMA polymer, imaging, in vivo, nanoparticles, persistent luminescence, surface coating,
- Publication type
- Journal Article MeSH
Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio. The hydrolytic degradation was proved for both the star copolymers containing either dendron or dendrimer core, showing the spontaneous hydrolysis in duration of few weeks. Finally, it was shown that the therapy with the biodegradable star conjugate with attached doxorubicin strongly suppresses the tumour growth in mice and is fully curative in most of the treated animals at dose corresponding approximately to one fourth of maximum tolerated dose (MTD) value. Both new biodegradable systems show superior efficacy and tumour accumulation over the first generation of star copolymers containing non-degradable PAMAM core.
- Keywords
- Cancer, Doxorubicin, Drug delivery, HPMA, Star-like polymers, bisMPA,
- MeSH
- Acrylamides MeSH
- Biocompatible Materials * MeSH
- Doxorubicin MeSH
- Pharmaceutical Preparations * MeSH
- Drug Delivery Systems MeSH
- Methacrylates MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Drug Carriers MeSH
- Polymers MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Acrylamides MeSH
- Biocompatible Materials * MeSH
- Doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Browser
- Pharmaceutical Preparations * MeSH
- Methacrylates MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- Drug Carriers MeSH
- Polymers MeSH