Most cited article - PubMed ID 30075311
Nanotherapeutics with suitable properties for advanced anticancer therapy based on HPMA copolymer-bound ritonavir via pH-sensitive spacers
Photo/radiosensitizers, such as octahedral molybdenum clusters (Mo6), have been intensively studied for photodynamic applications to treat various diseases. However, their delivery to the desired target can be hampered by its limited solubility, low stability in physiological conditions, and inappropriate biodistribution, thus limiting the therapeutic effect and increasing the side effects of the therapy. To overcome such obstacles and to prepare photofunctional nanomaterials, we employed biocompatible and water-soluble copolymers based on N-(2-hydroxypropyl)methacrylamide (pHPMA) as carriers of Mo6 clusters. Several strategies based on electrostatic, hydrophobic, or covalent interactions were employed for the formation of polymer-cluster constructs. Importantly, the luminescent properties of the Mo6 clusters were preserved upon association with the polymers: all polymer-cluster constructs exhibited an effective quenching of their excited states, suggesting a production of singlet oxygen (O2(1Δg)) species which is a major factor for a successful photodynamic treatment. Even though the colloidal stability of all polymer-cluster constructs was satisfactory in deionized water, the complexes prepared by electrostatic and hydrophobic interactions underwent severe aggregation in phosphate buffer saline (PBS) accompanied by the disruption of the cohesive forces between the cluster and polymer molecules. On the contrary, the conjugates prepared by covalent interactions notably displayed colloidal stability in PBS in addition to high luminescence quantum yields, suggesting that pHPMA is a suitable nanocarrier for molybdenum cluster-based photosensitizers intended for photodynamic applications.
- Keywords
- octahedral molybdenum clusters, photodynamic therapy, polymer carrier,
- Publication type
- Journal Article MeSH
Targeted drug delivery using nano-sized carrier systems with targeting functions to malignant and inflammatory tissue and tailored controlled drug release inside targeted tissues or cells has been and is still intensively studied. A detailed understanding of the correlation between the pharmacokinetic properties and structure of the nano-sized carrier is crucial for the successful transition of targeted drug delivery nanomedicines into clinical practice. In preclinical research in particular, fluorescence imaging has become one of the most commonly used powerful imaging tools. Increasing numbers of suitable fluorescent dyes that are excitable in the visible to near-infrared (NIR) wavelengths of the spectrum and the non-invasive nature of the method have significantly expanded the applicability of fluorescence imaging. This chapter summarizes non-invasive fluorescence-based imaging methods and discusses their potential advantages and limitations in the field of drug delivery, especially in anticancer therapy. This chapter focuses on fluorescent imaging from the cellular level up to the highly sophisticated three-dimensional imaging modality at a systemic level. Moreover, we describe the possibility for simultaneous treatment and imaging using fluorescence theranostics and the combination of different imaging techniques, e.g., fluorescence imaging with computed tomography.
- Keywords
- drug delivery, fluorescence imaging, noninvasive imaging, polymers, theranostics,
- Publication type
- Journal Article MeSH
- Review MeSH