<p>Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy</p>

Abstract

Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential. Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1 H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles. Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity. Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.

Associating resistance to immune checkpoint inhibitors with immunological escape in colorectal cancer

“…Continuous angiogenesis, one of the features of tumor development, plays a driving role in the process of TME shift in the direction of immune escape occurrence (118). Rapid tumor proliferation is always accompanied by angiogenesis to meet the needs of tumor cells for oxygen and nutrition (126). Additionally, tumor cells' aberrant angiogenesis is unable to carry enough oxygen.…”

Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy

“…A mixed solution of red blood cell suspension (1.25 mL) and ultrapure water (1.25 mL) was set as the positive control. After incubation for 3 h at 37 °C and centrifugation (1500 rpm, 15 min), the absorbance of the supernatant at 540 nm was measured by an ultraviolet–visible spectrophotometer (Yang et al., 2020 ). Percent hemolysis was calculated according to the following equation.…”

Broad-Spectrum Theranostics and Biomedical Application of Functionalized Nanomaterials

“…The resveratrol derivative is 3,5,4′-trimethoxy-trans-stilbene (BTM) and it is loaded in the PEG–PE micelles acting against colon cancer cells (CT26 cells) reporting anti-cancer efficacy and in tumor-bearing mice with an improved half-life and increased bioavailability [ 17 ]. Paclitaxel was effectively delivered to the tumor site with the help of the folic acid-hyaluronic acid-SS-vitamin E succinate polymer which enhanced selective targeted toxicity to the cancer cells without damaging healthy cells by analyzing cytotoxicity, apoptosis and cellular uptake studies in MCF-7 and NIH3T3 cells [ 18 ]. Studying the retention effects and skin penetration of thiolatedpluronic f127 polymeric micelles loaded with berberine using in vitro transdermic and fluorescence microscopy analysis showed that preparations enhanced the therapeutic benefit by decreasing the entry of drugsinto the systemic circulation, thereby preventing side effects and effectively treatinglocal skin diseases [ 19 ].…”