科研之友
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摘要
The acidosis of tumor microenvironments is one of the universal phenomena of solid tumors, and the increased acidity may be in fact essential intermediates in the progression of tumor growth and several lethal phenotypic traits of tumors, such as invasion and metastasis. Acid-labile polymers PBELA with incorporating acetal groups into biodegradable backbone of poly(D,L-lactide)-poly(ethylene glycol) (PELA) were utilized to load hydroxycamptothecin (HCPT) into electrospun fibers for intratumoral chemotherapy. Compared with that under a simulated physiological condition of pH 7.4, the incubation of PBELA fibers in acidic media resulted in larger mass loss and molecular weight reduction of fiber matrices and enhanced HCFT release from fibers. In vitro cytotoxicity assay of HCPT-loaded PBELA fibers indicated 6-fold higher inhibitory activity against HepG2 cells after incubation in pH 6.8 media than that of pH 7.4, while there was no significant difference for free HCPT and HCPT-loaded PELA fibers. The tumor growth, tumor cell apoptosis, and animal survival rate after intratumoral implantation of HCPT-loaded PBELA fibers indicated a superior in vivo antitumor activity and fewer side effects than other treatment. Therefore, acid-labile electrospun fibers may be promising implants for localized therapy of inoperable tumors and for prevention of post-surgical tumor recurrence.
