A Nanoplatform with Precise Control over Release of Cargo for Enhanced Cancer Therapy

Abstract

The development of a nanocarrier delivery system having both sufficient stability in blood circulation and a rapid drug release profile at target sites remains a major challenge in cancer therapy. Here, a multifunctional star-shaped micellar system with a precisely spatiotemporal control of releasing encapsulated agents is developed by mixing a photoinitiated crosslinking amphiphilic copolymer with a phenylboronic acid (PBA)-functionalized redox-sensitive amphiphilic copolymer for the first time. The combination of the functional polymers effectively resolves the contradiction that the micellar system cannot release the rapid drug release in cells when it possesses an extreme stability that is often required in blood circulation. In this system, the inner core polymers are photo-crosslinked, endowing a stable micelle matrix structure; the end groups of the hydrophilic segments are decorated with PBA ligands, providing an active targeting ability; disulfide bonds in the micellar matrix impart a redox-responsive trigger for the prompt intracellular release of drugs. As a result, with a relatively low DOX dosage (2 mg kg(-1) per injection) the in vivo antitumor effect on H22-bearing BALB/c mice shows that the micelles have a high therapeutic efficacy against solid tumors while minimal side effects against normal tissues.

Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical‐Structured Fiber Device for Overcoming Cancer Multidrug Resistance

“…Additionally, the active targeting micelle‐containing group, DOX‐PM+AP@F, had a slightly stronger fluorescence intensity than that of DOX‐M+AP@F without active targeting, which may be ascribed to that the receptor‐mediated specific internalization of DOX‐loaded micelles. [12b,c,18] The corresponding CLSM images in Figure c are in agreement with the result of flow cytometry. In general, the dual drug–loaded hierarchical‐structured electrospun fiber can successfully codeliver drugs into the tumor cells and DOX accumulation can be increased with the help of AP, which would overcome the drug resistance of MCF‐7/ADR tumor cells.…”

A Multifunctional Micellar Nanoplatform with pH‐Triggered Cell Penetration and Nuclear Targeting for Effective Cancer Therapy and Inhibition to Lung Metastasis

“…Meanwhile, the free HCPT group did not show a satisfactory tumor suppression efficacy, as the tumor volume was ≈0.87 cm 3 , which was 4.8 times as big as that of the PECL/DA‐Tat‐M group. In addition, the body weight of the mice treated with different samples all maintained an upward tendency (Figure c), reflecting that HCPT exhibited a relative lower systematic toxicity than some other antitumor therapeutics, such as doxorubicin . These results demonstrated that the therapeutic efficacy of PECL/DA‐Tat‐M was better than the other groups.…”

Rosin-based block copolymer intracellular delivery nanocarriers with reduction-responsive sheddable coronas for cancer therapy

“…38,39 Compared with other sheddable micelles, the release of Dox for the rosin-based ssP micelles in the presence of 10 mM GSH appeared to be slower 46,47,50 or competitive. Upon the reductive cleavage of disulfide linkages at the core/corona interfaces in response to GSH, Dox-loaded micelles are destabilized.…”

“…13,14 A particular cellular trigger is the reductive reaction associated with the presence of glutathione (GSH). [37][38][39] Furthermore, such reductionresponsive detachment of hydrophilic coronas, particularly poly(ethylene glycol) (PEG), has been significantly explored for gene delivery applications where PEG-stabilized micelloplexes are interacted with nucleic acids. Besides such a large redox potential difference, the elevated concentration in cancer cells makes GSH an effective intracellular trigger for reduction-responsive degradable nanocarriers.…”