Dual-responsive doxorubicin-loaded nanomicelles for enhanced cancer therapy

Abstract

Background: The enhancement of tumor retention and cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform, armed with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS)-induced drug release, is constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle. Results: The surface charge of this system was converted from negative to positive from pH 7.4 to pH 6.8, which facilitated the cellular uptake. In addition, methionine-based system was dissociated in a ROS-rich and acidic intracellular environment, resulting in the release of DOX and α-tocopheryl succinate (TOS). Then, the exposed TOS segments further induced the generation of ROS, leading to self-amplifiable disassembly of the micelles and drug release. Conclusions: We confirms efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro . The system exhibits outstanding tumor inhibition capability in vivo , indicating that dual stimuli nano-system has great potential to function as an anticancer drug delivery platform.

Carbon monoxide therapy: a promising strategy for cancer

“…19,63 For cancer patients, chemotherapy is a primary means of cancer treatment. Currently, the commonly used chemotherapeutic drugs include doxorubicin, [64][65][66][67][68][69] platinum drugs, [70][71][72] fluorouracil, [73][74][75] paclitaxel, [76][77][78] etc. However, the lack of species distribution and rapid elimination of chemotherapeutic drugs in the body are problems that cause severe toxic side effects.…”

Stimuli‐responsive polypeptide nanoassemblies: Recent progress and applications in cancer nanomedicine

“…The modified DMA in PLL side chains enables the nanodrug pHe‐sensitivity, during which process those negative nanodrugs were converted to positive ones from pH 7.4 to pH 6.8, facilitating cell internalization. Especially, the modified methionine‐DMA groups in PLL side chains were oxidized and cleaved in high ROS and acidic pHe media, resulting in a sharp DOX release and the exposure of TOS; the exposed TOS groups were beneficial to the generation of ROS, which lead to self‐amplifiable micellar disintegration and DOX release (X. Zhang, Zhu, et al, 2020). In vivo, PPT/D(DMA)@DOX induced the highest tumor suppression activity, demonstrating a synergistic antitumor effect between TOS and DOX (Figure 4).…”

“…(c) Tumor volume over the treatment time. Reprinted with permission from X. Zhang, Zhu, et al (2020). Copyright 2020.…”