Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy.

Nanomedicines have been designed and developed to deliver anticancer drugs or exert anticancer therapy more selectively to tumor sites. Recent investigations have gone beyond delivering drugs to tumor tissues or cells, but to intracellular compartments for amplifying therapy efficacy. Mitochondria are attractive targets for cancer treatment due to their important functions for cells and close relationships to tumor occurrence and metastasis. Accordingly, multifunctional nanoplatforms have been constructed for cancer therapy with the modification of a variety of mitochondriotropic ligands, to trigger the mitochondria-mediated apoptosis of tumor cells. On this basis, various cancer therapeutic modalities based on mitochondria-targeted nanomedicines are developed by strategies of damaging mitochondria DNA (mtDNA), increasing reactive oxygen species (ROS), disturbing respiratory chain and redox balance. Herein, in this review, we highlight mitochondria-targeted cancer therapies enabled by nanoplatforms including chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiodynamic therapy (RDT) and combined immunotherapy, and discussed the ongoing challenges.

Near-infrared light and magnetic field dual-responsive porous silicon-based nanocarriers to overcome multidrug resistance in breast cancer cells with enhanced efficiency.

The development of drug delivery systems based on external stimuli-responsive nanocarriers is important to overcome multidrug resistance in breast cancer cells. Herein, iron oxide/gold (Fe3O4/Au) nanoparticles were first fabricated via a simple hydrothermal reaction, and subsequently loaded into porous silicon nanoparticles (PSiNPs) via electrostatic interactions to construct PSiNPs@(Fe3O4/Au) nanocomposites. The as-prepared PSiNPs@(Fe3O4/Au) nanocomposites exhibited excellent super-paramagnetism, photothermal effect, and T2-weight magnetic resonance imaging capability. In particular, with the help of a magnetic field, the cellular uptake of PSiNPs@(Fe3O4/Au) nanocomposites was significantly enhanced in drug-resistant breast cancer cells. Moreover, PSiNPs@(Fe3O4/Au) nanocomposites as carriers showed a high loading and NIR light-triggered release of anticancer drugs. Based on the synergistic effect of magnetic field-enhanced cellular uptake and NIR light-triggered intracellular release, the amount of anticancer drug carried by PSiNPs@(Fe3O4/Au) nanocarriers into the nuclei of drug-resistant breast cancer cells sharply increased, accompanied by improved chemo-photothermal therapeutic efficacy. Finally, PSiNPs@(Fe3O4/Au) nanocomposites under the combined conditions of magnetic field attraction and NIR light irradiation also showed improved anticancer drug penetration and accumulation in three-dimensional multicellular spheroids composed of drug-resistant breast cancer cells, leading to a better growth inhibition effect. Overall, the fabricated PSiNPs@(Fe3O4/Au) nanocomposites demonstrated great potential for the therapy of multidrug-resistant breast cancer in future.

Multifunctional Chitosan/Porous Silicon@Au Nanocomposite Hydrogels for Long-Term and Repeatedly Localized Combinatorial Therapy of Cancer via a Single Injection.

Considering the future clinical applications of localized cancer therapy, it is of great importance to construct injectable biodegradable nanocomposite hydrogels with combinatorial therapeutic efficacy. Here, porous silicon nanoparticles (PSiNPs) as host matrix were chosen to fabricate PSiNPs@Au nanocomposites via in situ reductive synthesis of gold nanoparticles. Then PSiNPs@Au nanocomposites were further incorporated into thermosensitive chitosan (CS) hydrogels to construct CS/PSiNPs@Au nanocomposite hydrogels, which showed in situ gelation at physiological temperature, excellent biodegradability, and biocompatibility. Especially with the encapsulation of CS hydrogels, PSiNPs@Au nanocomposites had a long-term stable photothermal effect with higher local temperature under near-infrared (NIR) laser irradiation, whether in vitro or in vivo. Besides, assisted by NIR laser irradiation, CS/PSiNPs@Au nanocomposite hydrogels exhibited a long-term sustained release of anticancer drugs (doxorubicin hydrochloride, DOX) in acidic tumor environments. Finally, DOX/CS/PSiNPs@Au precursors were administrated into tumor-bearing mice via a single intratumoral injection, which presented a significant synergistic chemo-photothermal therapeutic efficacy under repeated NIR laser irradiation during long-term cancer treatments. Accordingly, we developed a novel strategy to prepare multifunctional CS/PSiNPs@Au nanocomposite hydrogels and also demonstrated their potential applications in localized cancer therapy in future clinics.