Theranostic Prodrug Vesicles for Reactive Oxygen Species‐Triggered Ultrafast Drug Release and Local‐Regional Therapy of Metastatic Triple‐Negative Breast Cancer

Abstract

A reactive oxygen species (ROS)-activatable doxorubicin (Dox) prodrug vesicle (RADV) is presented for image-guided ultrafast drug release and local-regional therapy of the metastatic triple-negative breast cancer (TNBC). RADV is prepared by integrating a ROS-activatable Dox prodrug, a poly(ethylene glycol) (PEG)-modified photosensitizer pyropheophorbide-a, an unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine, and cholesterol into one single nanoplatform. RADV is of extremely high drug loading ratio (27.5 wt%) by selfassembly of the phospholipid-mimic Dox prodrug into the liposomal bilayer membrane. RADV displays good colloidal stability to prevent premature drug leakage during the blood circulation and inert photochemotoxicity to avoid nonspecific side effect. RADV passively accumulates at tumor site through the enhanced permeability and retention effect when administrated systemically. Once deposited at the tumor site, RADV generates fluorescent and photoacoustic signals to guide near-infrared (NIR) laser irradiation, which can induce localized ROS generation, not only to trigger prodrug activation and ultrafast drug release but also conduct photodynamic therapy in a spatiotemporally controlled manner. In combination with NIR laser irradiation, RADV efficiently inhibits the tumor growth and distant metastasis of TNBC. Local-regional tumor therapy using intelligent theranostic nanomedicine might provide an alternative option for highly efficient treatment of the metastatic TNBC.

Rational Design of Nanoparticles with Deep Tumor Penetration for Effective Treatment of Tumor Metastasis

“…We developed a multifunctional micelle with efficient production of singlet oxygen upon laser irradiation to improve their deep penetration for enhancement of therapeutic effects . Moreover, the generation of reactive oxygen species (ROS) upon laser irradiation has been used to trigger intra‐tumoral extravasation and deep penetration of liposomes for treatment of triple‐negative breast cancer . Specifically, Xie and co‐workers exploited ferritin nanocages as a photosensitizer carrier with selective targeting of CAFs .…”

Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers

“…Therefore, these chemo-photodynamic therapies are simply combinations of the two therapies and do not confer synergistic effects of PS and chemotherapy drugs, making them insufficient for amplifying the anticancer efficacy. Increasing evidence has demonstrated that nanocarriers should boost the intracellular release of cytotoxic drug during the PDT process to yield the maximal benefit of chemo-photodynamic therapy 22 - 27 . Liu et al demonstrated that the mesoporous silica nanorods with SO-sensitive shells offer remarkable synergistic therapeutic effects in cancer treatment owing to the boosted release of DOX specifically at the tumor site during the light-induced PDT process 28 .…”

Sensors, Imaging Agents, and Theranostics to Help Understand and Treat Reactive Oxygen Species Related Diseases

“…Poly‐prodrug nanoparticles of doxorubicin have been constructed. For example, Li and co‐workers developed a prodrug vesicle based on the thioketal linkage for local‐regional therapy of metastatic triple‐negative breast cancer. The system was triggered by light irradiation (producing ROS) for combined chemo‐ and photodynamic therapy.…”