A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy.

The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system(M@C-HA/ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while M@C-HA/ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen (1O2) under irradiation of an 808 nm laser, realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy. Specially, we also investigated the relationship of singlet oxygen (1O2) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an "all active" delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.

Current trends in smart mesoporous silica-based nanovehicles for photoactivated cancer therapy.

Photoactivated therapeutic strategies (photothermal therapy and photodynamic therapy), due to the adjusted therapeutic area, time and light dosage, have prevailed for the fight against tumors. Currently, the monotherapy with limited treatment effect and undesired side effects is gradually replaced by multimodal and multifunctional nanosystems. Mesoporous silica nanoparticles (MSNs) with unique physicochemical advantages, such as huge specific surface area, controllable pore size and morphology, functionalized modification, satisfying biocompatibility and biodegradability, are considered as promising candidates for multimodal photoactivated cancer therapy. Excitingly, the innovative nanoplatforms based on the mesoporous silica nanoparticles provide more and more effective treatment strategies and display excellent antitumor potential. Given the rapid development of antitumor strategies based on MSNs, this review summarizes the current progress in MSNs-based photoactivated cancer therapy, mainly consists of (1) photothermal therapy-related theranostics; (2) photodynamic therapy-related theranostics; (3) multimodal synergistic therapy, such as chemo-photothermal-photodynamic therapy, phototherapy-immunotherapy and phototherapy-radio therapy. Based on the limited penetration of irradiation light in photoactivated therapy, the challenges faced by deep-seated tumor therapy are fully discussed, and future clinical translation of MSNs-based photoactivated cancer therapy are highlighted.

Polydopamine-carbon dots functionalized hollow carbon nanoplatform for fluorescence-imaging and photothermal-enhanced thermochemotherapy.

The low power photothermal therapy can reduce the tissue damage caused by laser irradiation, thus the near-infrared (NIR) absorbing vehicles with high photothermal conversion efficiency are demanded in the low power treatment. Herein, the NIR-absorbing agent polydopamine (PDA) and carbon dots (CDs) were gated on the openings of hollow mesoporous carbon (HMC) to construct a photothermal enhanced multi-functional system (HMC-SS-PDA@CDs). Interestingly, the fluorescence emission wavelength of HMC-SS-PDA@CDs was red-shifted by FRET effect between PDA and CDs, which solved the dilemma of fluorescence quenching of carbon-based materials and was more conducive to cell imaging. The modification of PDA@CDs not only acts as the gatekeepers to realize multi-responsive release of pH, GSH and NIR, but also endows the HMC vehicle with excellent photothermal generation capacity, the possibility for bio-imaging as well as the enhanced stability. Naturally, both the cytological level and the multicellular tumor sphere level demonstrate that the delivery system has good low-power synergistic therapeutic with combination index (CI) of 0.348 and imaging effects. Meanwhile, the combined treatment group showed the highest tumor inhibition rate of 92.6% at 0.75 W/cm2. Therefore, DOX/HMC-SS-PDA@CDs nano-platform had broad application prospects in low power therapy and convenient imaging of carbon-based materials.

Triple stimuli-responsive ZnO quantum dots-conjugated hollow mesoporous carbon nanoplatform for NIR-induced dual model antitumor therapy.

Aiming at the inefficiency and toxicity in traditional antitumor therapy, a novel multifunctional nanoplatform was constructed based on hollow mesoporous carbon (HMC) to achieve triple stimuli response and dual model antitumor therapy via chemo-photothermal synergistic effect. HMC was used as an ideal nanovehicle with a high drug loading efficiency as well as a near-infrared (NIR) photothermal conversion agent for photothermal therapy. Acid-dissoluble, luminescent ZnO quantum dots (QDs) were used as the proper sealing agents for the mesopores of HMC, conjugated to HMC via disulfide linkage to prevent drug (doxorubicin, abbreviated as Dox) premature release from Dox/HMC-SS-ZnO. After cellular endocytosis, the Dox was released in a pH, GSH and NIR laser triple stimuli-responsive manner to realize accurate drug delivery. Moreover, the local hyperthermia effect induced by NIR irradiation could promote the drug release, enhance cell sensitivity to chemotherapeutic agents, and also directly kill cancer cells. As expected, Dox/HMC-SS-ZnO exhibited a high drug loading capacity of 43%, well response to triple stimuli and excellent photothermal conversion efficiency η of 29.7%. The therapeutic efficacy in 4T1 cells and multicellular tumor spheroids (MCTSs) demonstrated that Dox/HMC-SS-ZnO + NIR had satisfactory chemo-photothermal synergistic effect with a combination index (CI) of 0.532. The cell apoptosis rate of the combined treatment group was more than 95%. The biodistribution and pharmacodynamics studies showed its biosecurity to normal tissues and synergistic inhibition effect to tumor cells. These distinguished results indicated that the Dox/HMC-SS-ZnO nanoplatform is potential to realize efficient triple stimuli-responsive drug delivery and dual model chemo-photothermal synergistic antitumor therapy.

Multi-stimuli responsive nanosystem modified by tumor-targeted carbon dots for chemophototherapy synergistic therapy.

In this work, a tumor-targeted and multi-stimuli responsive drug delivery system combining infrared thermal imaging of cells with thermo-chemotherapy was developed. Oxidized mesoporous carbon nanoparticles (MCNs-COOH) with high photothermal conversion ability (photothermal transduction efficiency η = 27.4%) in near-infrared (NIR) region were utilized to encapsulate doxorubicin (DOX). The outer surfaces of MCNs-COOH were capped with multifunctional carbon dots (CDHA) as simultaneous smart gatekeepers, a tumor targeting moiety and a fluorescent probe. NIR laser irradiation killed cancer cells through NIR-light induced hyperthermia, facilitated chemotherapeutic drug release and enhanced the sensitivity of tumor cells to drugs. The therapeutic efficacy in two-dimensional (2D) and three-dimensional (3D) cells demonstrated that MC-CDHA loading DOX (MC-CDHA/DOX) had good chemo-photothermal synergistic antitumor effects (combination index of CI = 0.448). The biodistribution and pharmacodynamics experiments of MC-CDHA/DOX in the 4T1 tumor model indicated that MCNs-COOH prolonged the residence time of DOX in tumor tissues and therefore actualized effective synergistic photothermal chemotherapy. By combining these excellent capabilities, the tumor-targeted and multi-stimuli responsive drug delivery system can be utilized as a visible nanoplatform for chemophotothermal synergistic therapy.