Near-Infrared Light-Activated Dual Targeting with Peptide-Conjugated Mesoporous Silica Nanoparticles for Multimodal Anticancer Therapy

The nuclear-targeted delivery system (NTDS) is one of the major advancements in drug delivery. It acts efficiently by specifically destroying cancer cells. On mesoporous silica nanoparticles (MSNs), a trans-activator of transcription peptide was conjugated. A targeted multifunctional NTDS is a novel form of nanotherapeutics, where the drug is selectively targeted to specific cell nuclei. Herein, we have successfully fabricated a cervical cancer receptor and nuclear targeting formulation of MSNs integrated with paclitaxel (PTX) and indocyanine green (ICG), thus forming a novel composite denoted as NC. To successfully achieve NTDS, we have introduced an effective strategy for constructing a nuclear-targeted MSNs, which possesses an extraordinary photothermal effect to ablate the cancer cells and simultaneously inhibit recurrence in the tumor microenvironment. The NC rapidly increases the temperature of the nucleus and destroys genetic substances of cancer cells when exposed to an 808 nm near-infrared laser. Following that, PDT selectively destroys tumor cells by creating singlet oxygen species, which is paired with effective PTX-based treatment. Photothermally ablated tumor cells can induce the immunogenic cell death (ICD) of tumor cells with the release of tumor-associated antigens and damage-associated molecular patterns (DAMPs). ICD markers include the release of HMGB1, ATP, and CRT. To address the restrictions of NC, an anti-PD-L1-activated nanosystem was developed to potentiate the antitumor efficacy along with photo/chemo/immunotherapy. Therefore, multimodal combinatorial therapy will be more effective on tumors and will reduce tumor recurrence. This work provides vital guidance for MSNs-based PTT/PDT/chemo/immunotherapy applications in cancer therapy.