Dataset Information

Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.

ABSTRACT: Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol-gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs-hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs-hydrogel may have potential clinical applications.

SUBMITTER: Fan R

PROVIDER: S-EPMC4672756 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.

Fan Rangrang R Tong Aiping A Li Xiaoling X Gao Xiang X Mei Lan L Zhou Liangxue L Zhang Xiaoning X You Chao C Guo Gang G

International journal of nanomedicine 20151203

Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+ ...[more]

PMID: 26664119

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Project description:Nanoparticle-loaded hydrogels - localized drug delivery devices containing a combination of therapeutic nanoparticles and implantable hydrogel - have been recipients of increased focus and interest for cancer treatment. However, it is difficult for the released nanoparticles to penetrate deeply into tumors because of the dense collagen network in the tumor extracellular matrix, which greatly limits their antitumor effect. We hypothesized that the implantation of a hydrogel loaded with both nanoparticles and losartan (Los) might enhance penetration because Los has been proven to effectively reduce collagen levels in various tumors. Herein, we developed a nanoparticle/Los-loaded hydrogel system and evaluated the intratumoral distribution and anticancer effect after peritumoral implantation of nanoparticles. Fluorescent polystyrene nanoparticles (FPNPs, size ~100 nm) and Los were simultaneously encapsulated in a polyethylene glycol (PEG) hydrogel to form the FPNP/Los-loaded hydrogel. After peritumoral implantation in 4T1 tumor-bearing mice for 2 weeks, intratumoral distributions of FPNPs and collagen level were determined. Based on the results, liposomal doxorubicin (Doxil, ~100 nm) was subsequently substituted for FPNPs in the hydrogel. The cellular uptake and cytotoxicity of the Doxil/Los-loaded hydrogel were studied, and the in vivo antitumor efficacy after peritumoral implantation was evaluated. Compared with a standard FPNP-loaded hydrogel, the FPNP/Los-loaded hydrogel resulted in enhanced penetration and reduced collagen levels after implantation. Thereafter, the potential of a Doxil/Los-loaded hydrogel for cancer treatment was studied. Doxorubicin was released from the hydrogel and induced effective cytotoxicity against 4T1 cells. The Doxil/Los-loaded hydrogel showed synergistic antitumor effects in 4T1 tumor-bearing mice and was more effective at tumor inhibition than the Doxil-loaded hydrogel. This study provides a proof of principle that the implantation of nanoparticles/Los-loaded hydrogel can increase the intratumoral distribution and antitumor efficacy of nanoparticles, owing to collagen depletion by Los. Future studies may build on this strategy for enhanced tumor penetration of nanoparticles.

Dataset Information

Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.

Publications

Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.

Similar Datasets

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