In the cutting-edge field of cancer therapy, noninvasive photothermal therapy (PTT) has received great attention because it is considered to overcome the drawbacks of conventional surgery, radiotherapy and chemotherapy of severe body injuries and side effects on the immune system. The construction of PTT therapeutic and theranostic nanoplatforms is the key issue in achieving tumor targeting, imaging and therapy in a synergetic manner. In this review, we focus on the recent advances in constructing PTT therapeutic and theranostic nanoplatforms by integrating nanomaterials and functional polymers. The noninvasive photothermal cancer therapy mechanism and achievement strategies of PTT therapeutic and theranostic nanoplatforms are presented as well as the innovative construction strategies and perspectives for the future. Owing to their high tumor ablation efficiency, biological availability and low- or non-toxicity, PTT therapeutic and theranostic nanoplatforms are promising and emerging in medicine and clinical applications.
We present a novel glutathione-responsive amphiphilic drug self-delivery (DSD) micelle with one-pot synthesis to synergistically address the problems of controlled drug release, degradability, drug tracing and in vivo accumulated toxicity.
In this study, we present a novel drug self-assembled delivery system (DSDs) with pH and glutathione dual responsiveness to synergistically address the problems of traditional polymer-based carriers, i.e., their low drug loading efficiency, poor biocompatibility and nonbiodegradability. The DSD system with minimum assistant substances was developed from methotrexate (MTX) model drug copolymers and polyethylene glycol (PEG), which gives the system a higher drug loading efficiency and completely avoids the use of toxic carriers. The amphiphilic block copolymers of MTX and PEG are self-assembled into stable micelles such that MTX can be delivered to tumor tissues in vivo and controllable release can be achieved for cancer therapy via the cleavage of the reversible covalent bonds in the copolymer. The micelles overlapped with lysosomes for cellular uptake, and the in vivo distribution was higher in tumor tissues. Biological evaluation and histological analysis confirmed that the DSD micelles were more effective in killing tumor cells than free MTX. In addition, there were fewer side effects in normal tissues. As a result, tumor growth could be effectively inhibited in vivo. The DSDs concept is a perfect emerging strategy to address the problems of traditional polymer-based anticancer drug carriers in a synergetic manner and offers new potential routes of cancer therapy and clinical treatments.
Amphiphilic hyperbranched polyprodrugs (DOX-S-S-PEG) with drug repeat units in hydrophobic core linked by disulfide bonds were developed as drug self-delivery systems for cancer therapy. The hydroxyl groups and the amine group in doxorubicin (DOX) were linked by 3,3'-dithiodipropanoic acid as hydrophobic hyperbranched cores, then amino-terminated polyethylene glycol monomethyl ether (mPEG-NH ) as hydrophilic shell was linked to hydrophobic cores to form amphiphilic and glutathione (GSH)-responsive micelle of hyperbranched polyprodrugs. The amphiphilic micelles can be disrupted under GSH (1 mg mL ) circumstance. Cell viability of A549 cells and 293T cells was evaluated by CCK-8 and Muse Annexin V & Dead Cell Kit. The disrupted polyprodrugs maintained drug activity for killing tumor cells. Meanwhile, the undisrupted polyprodrugs possessed low cytotoxicity to normal cells. The cell uptake experiments showed that the micelles of DOX-S-S-PEG were taken up by A549 cells and distributed to cell nuclei. Thus, the drug self-delivery systems with drug repeat units in hydrophobic cores linked by disulfide bonds showed significant special advantages: 1) facile one-pot synthesis; 2) completely without toxic or non-degradable polymers; 3) DOX itself functions as fluorescent labeled molecule and self-delivery carrier; 4) drug with inactive form in hyperbranched cores and low cytotoxicity to normal cells. These advantages make them excellent drug self-delivery systems for potential high efficient cancer therapy.
The biocompatible amphiphilic block copolymers and the CPT model drug were self-assembled into micelles with bright fluorescence and taken up by tumor cells. Then, the disulfide bonds in the micelles were cleaved to release CPT at a high GSH concentration.
Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. In this work, two types of CPT-conjugated polymers were synthesized based on poly(β-L-malic acid) (PMLA) derivatives. Folic acid (FA) was introduced into the polymers as tumor targeting group. The micellization behaviors of these polymers and antitumor activity of different self-assembled micelles were investigated. Results indicate that poly(ethylene glycol)-poly(β-L-malic acid)-campotothecin-I (PEG-PMLA-CPT-I, P1) is a grafted copolymer, and could form star micelles in aqueous solution with a diameter of about 97 nm, also that PEG-PMLA-CPT-II (P2) is an amphiphilic block copolymer, and could form crew cut micelles with a diameter of about 76 nm. Both P1 and P2 micelles could improve the cellular uptake of CPT, especially the FA-modified micelles, while P2 micelles showed higher stability, higher drug loading efficiency, smaller size, and slower drug release rate than that of P1 micelles. These results suggested that the P2 (crew cut) micelles possess better stability than that of the P1 (star) micelles and might be a potential drug delivery system for cancer therapy.
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