Charge and Size Dual Switchable Nanocage for Novel Triple‐Interlocked Combination Therapy Pattern. Issue 18 (4th August 2020)

• Record Type: Journal Article
• Authors: Yang, Rui; Zhang, Zipeng; Fu, Shunli; Hou, Teng; Mu, Weiwei; Liang, Shuang; Gao, Tong; Guan, Li; Fang, Yuxiao; Liu, Yongjun; Zhang, Na
• Is Part Of: Advanced science. Volume 7:Issue 18(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-04
• Subjects: dual switchable nanocages -- deep tumor penetration -- pH‐triggered release -- triple‐interlocked combination therapy -- tumor‐associated macrophage repolarization; Science -- Periodicals; 505
• DOI: 10.1002/advs.202000906
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH‐triggered charge and size dual switchable nanocage co‐loaded with abemaciclib and IMD‐0354 (PA/PI‐ND) is reported, exhibiting a novel triple‐interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy. The charge reversal polymer NGR‐poly(ethylene glycol)‐poly(l ‐lysine)‐dimethylmaleic anhydride (NGR‐PEG‐PLL‐DMA, ND) in PA/PI‐ND promotes the pH‐triggered charge reversal from negative to positive and size reduction from about 180 to 10 nm in an acidic tumor microenvironment, which greatly enhances cellular uptake and tumor tissue deep penetration. With the PA/PI‐ND triple‐interlocked combination therapy, the chemotherapeutic effect is enhanced by the action of abemaciclib to induce cell cycle arrest in the G1 phase, together with the reduction in cyclin D levels caused by IMD‐0354. The dual anti‐tumor promoting immunotherapy is achieved by abemaciclib selectively inhibiting the proliferation of regulatory T cells (Tregs) and by IMD‐0354 promoting tumor‐associated macrophage (TAM) repolarization from an M2 to M1 phenotype. Furthermore, PA/PI‐ND has improved anti‐tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI‐ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy. Abstract : PA/PI‐ND can deliver to tumor tissues mediated by active ligand NGR. The interior PA and PI is released because of the switch of charge and size at the acidic tumor microenvironment to promote cellular uptake and deep penetration. PA/PI‐ND also pocesses a triple‐interlocked combination therapy pattern of chemotherapy, immunotherapy, and chemoimmunotherapy.