Benzylguanidine and Galactose Double-Conjugated Chitosan Nanoparticles with Reduction Responsiveness for Targeted Delivery of Doxorubicin to CXCR 4 Positive Tumors

• DOI: 10.1021/acs.bioconjchem.0c00496
• Publication Date: 2020-09-29T21:41:39Z
• Authors: Fei Kong; Cui Tang; Chunhua Yin
• Keywords: Nanocarriers

Benzylguanidine, a small cationic and amphiphilic molecule, exhibits high affinity to C-X-C chemokine receptor type 4 (CXCR 4) membrane penetration ability. It has not been used as functional moiety of nanocarriers for the systemic delivery chemotherapeutic drugs in tumor therapy. In this study, we investigated benzylguanidine-conjugated their efficiency safety targeted doxorubicin (DOX) CXCR positive tumors. We conjugated benzylguanidine bearing guanidinobenzoic acid onto cystamine bismethacrylamide cross-linked chitosan-poly(methyl methacrylate) nanoparticles, which were then decorated with lactobionic (abbreviated LGCC NPs). A proportion NPs able directly penetrate plasma enter cells, thereby circumventing endocytic vesicles. The DOX-loaded (LGCC NPs/DOX) displayed good stability under extracellular physiological conditions reduction-triggered drug release glutathione (GSH) concentration. Moreover, NPs/DOX showed an increase tumor-targeted cellular uptake through receptor-mediated endocytosis, enhanced endo/lysosomal escape, nuclear distribution. More importantly, significantly suppressed vitro vivo proliferation hepatocarcinoma breast cancer. findings provide guideline combined application other groups antitumor nanomedicines.