Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors

Photothermal therapy(PTT)has brought hope for cancer treatments,with hyperthermia-induced immunogenic cell death(ICD),which is a critical part of therapeutically induced antitumor immune responses.Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation,therefore demonstrating urgent requirements for ICD amplifier.Herein,a sub-10 nm supramolecular nanoassembly was formed by coassembly of clinically approved aluminum adjuvant and commonly used indocyanine green(ICG)under the assistance of lignosulfonate(LS,a green and sustainable multifunctional lignin derivative)for localized photothermal-immunotherapy of breast cancer.The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD,efficiently eliciting solid immune responses through dendritic cells(DCs)activation and cytotoxic T-cell responses initiation for tumor killing.Moreover,anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity.The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy,which shows promise for delivering other therapeutics in biomedical applications.

Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer.In present study,nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2(MMP-2)dual-responsive,tumor targeting,and size-variability were designed for enhancing the antitumor efficacy and achieving"on-demand"drug release markedly.Based on the thermal sensitivity of gelatin,we designed a size-variable gelatin nanoparticle(GNP)to encapsulate indocyanine green(ICG)and doxorubicin(DOX).Under an 808 nm laser irradiation,GNP-DOX/ICG responded photothermally and swelled in size from 71.58?4.28 to 160.80?9.51 nm,which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics.Additionally,GNP-DOX/ICG showed a size reduction of the particles to 33.24?4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor.In the subsequently performed in vitro experiments,it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic.Consequently,GNP-DOX/ICG could efficiently suppress the growth of 4 T1 tumor in vivo.In conclusion,this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.

Cooperative coordination-mediated multi-component self-assembly of“all-in-one”nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation,high drug-loading efficiency,and excellent therapeutic efficacy.Herein,MnAs-ICG nanospike was generated by self-assembly of indocyanine green(ICG),manganese ions(Mn^(2+)),and arsenate(AsO_(4)^(3−))based on electrostatic and coordination interactions,effectively integrating the bimodal imaging ability of magnetic resonance imaging(MRI)and fluorescence(FL)imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an“all-in-one”theranostic nano-platform.The as-prepared MnAs-ICG nanospike had a uniform size,well-defined nanospike morphology,and impressive loading capacities.The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability,enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components.In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect,prolonged blood circulation and increased tumor accumulation compared to their individual components,effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect.Taken together,this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.