Nowadays, photothermal therapy (PTT) utilizing photothermal conversion agents (PTAs) to generate sufficient heat under near-infrared (NIR) light irradiation for tumor ablation has attracted extensive ...research attention. Despite the great advancement, the therapeutic efficacy of PTT in tumor treatment is still compromised by several obstacles, such as low photothermal conversion efficiency, poor stability of PTAs, inadequate tumor accumulation and cellular uptake, and thermal-resistance of tumors, as well as tumor recurrence and metastasis. In this review, we highlight recent advances in nanomaterials that focus on overcoming the above obstacles and thus enhancing the therapeutic outcome of PTT. PTAs with improved photothermal performance and modification strategies for efficient PTT are summarized, which are further classified into three main types, utilizing activatable PTAs, improving the local concentration of PTAs, and overcoming intrinsic drawbacks of PTT (
e.g.
, heat shock responses). Furthermore, the limitations and challenges of nanomaterials for enhanced PTT are also discussed.
Recent advances in nanomaterials for enhanced therapeutic efficacy of photothermal therapy in tumor treatment were highlighted.
Covalent organic frameworks (COFs) with 2D π‐conjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy. Two molecules, ...5′,5′′′′‐(1,4‐phenylene)bis((1,1′:3′,1′′‐terphenyl‐4,4′′‐dicarbaldehyde)) (L‐3C) and 4,4′,4′′‐(1,4‐phenylene)bis((2,2′:6′,2′′‐terpyridine‐5,5′′‐dicarbaldehyde)) (L‐3N), inactive to generating reactive oxygen species (ROS), were linked to form two COFs, COF‐808 and COF‐909, respectively, exhibiting excellent ROS production efficiency. The high permanent porosity of these COFs (surface areas 2270 and 2610 m2 g−1) promoted diffusion of both oxygen and release of ROS in cells. This, combined with the excellent photostability and biocompatibility, led to excellent PDT performance. In vitro, over 80 % of tumor cells were killed after PDT treatment using COF‐909 at the concentration of 50 μg mL−1 for 150 s. In vivo, drastic reduction of tumor size was observed (from 9 mm to less than 1 mm) after 10 day treatment.
Covalent organic frameworks (COFs) with 2D π‐conjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy. Two molecules inactive to generating reactive oxygen species (ROS) were linked to form two COFs exhibiting excellent ROS production efficiency. The high permanent porosity of these COFs promoted both the diffusion of oxygen and the release of ROS in cells.
Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four ...kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non‐drug‐loaded nanoformulations (i.e., metal nanoparticles and molecular self‐assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task‐specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle‐targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re‐evaluation of this emerging field are presented.
The rapid development in the field of subcellular targeted cancer therapy is reviewed systemically and comprehensively on account of six sets of treatment modalities: chemotherapy, gene therapy, PDT, hyperthermia, non‐drug‐loaded nanoformulations, and synergistic combined therapy.
Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)‐camouflaged hollow MnO2 (HMnO2) catalytic nanosystem ...embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long‐circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2, which can be produced during the decomposition of endogenous H2O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti‐PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.
A strategy based on intra/extracellular lactic acid exhaustion is reported to achieve synergistic metabolic therapy and immunotherapy of tumors. This strategy is performed by a cascade catalytic nanosystem (PMLR) that integrates a hollow MnO2 nanocarrier with lactate oxidase and a glycolysis inhibitor.
Nanoscale metal–organic frameworks (nanoMOFs) are promising porous nanomaterials for diverse applications, such as catalysis, imaging, functional membranes, and drug delivery. At the nanoscale, the ...size of materials is critical for their properties and utility. Herein, a straightforward and convenient strategy is developed for size precisely controlled synthesis of nanoMOFs. Unlike other approaches, this strategy can directly give nanoMOFs of predicable sizes within a wide range without the time consuming trial‐and‐error process and without the addition of additives. In this approach, the preciseness of size control is ensured by the separated and controlled nucleation and growth. The size controlled synthesis of 9 kinds of most widely studied nanoMOFs confirms the versatility of this strategy. More importantly, this approach can be utilized for scale‐up synthesis of nanoMOFs with the same precise size control.
About the size of it: Homogeneous nanoscale metal–organic frameworks (nanoMOFs) of predicable size within a wide range are synthesized. The precise size control is ensured by the controlled nucleation and controlled growth in this strategy. This strategy is applicable for scale‐up synthesis of nanoMOFs with precise size control.
Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, are developed and used to treat different types of cancer. Recently, chemodynamic ...therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton‐like reaction to generate highly cytotoxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide (H2O2) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off‐target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies are implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H2O2 level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst‐mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed.
Chemodynamic therapy (CDT) can produce highly lethal hydroxyl free radicals via Fenton or Fenton‐like reaction. This review summarizes recent progress of nanocatalyst‐mediated CDT for antitumor application, highlights various strategies to improve the catalytic efficiency, and discusses the challenges and opportunities of CDT in the future.
Efficacy and safety of chemotherapeutic drugs constitute two major criteria in tumor chemotherapy. Nanomedicines with tumor‐targeted properties hold great promise for improving the efficacy and ...safety. To design targeted nanomedicines, the pathological characteristics of tumors are extensively and deeply excavated. Here, the rationale, principles, and advantages of exploiting these pathological characteristics to develop targeted nanoplatforms for tumor chemotherapy are discussed. Homotypic targeting with the ability of self‐recognition to source tumors is reviewed individually. In the meanwhile, the limitations and perspective of these targeted nanomedicines are also discussed.
Nanomedicines with tumor‐targeted properties hold great potential for improved efficacy and safety of tumor chemotherapy. This review summarizes the recent advances in exploiting tumor‐associated pathological features to elaborate tumor targeting nanomedicines. Homotypic targeting strategies are also discussed due to the self‐recognition to source tumors.
Multi‐component MOFs contain multiple sets of unique and hierarchical pores, with different functions for different applications, distributed in their inter‐linked domains. Herein, we report the ...construction of a class of precisely aligned flexible‐on‐rigid hybrid‐phase MOFs with a unique rods‐on‐octahedron morphology. We demonstrated that hybrid‐phase MOFs can be constructed based on two prerequisites: the partially matched topology at the interface of the two frameworks, and the structural flexibility of MOFs with acs topology, which can compensate for the differences in lattice parameters. Furthermore, we achieved domain selective loading of multiple guest molecules into the hybrid‐phase MOF, as observed by scanning transmission electron microscopy–energy‐dispersive X‐ray spectrometry elemental mapping. Most importantly, we successfully applied the constructed hybrid‐phase MOF to develop a dual‐drug delivery system with controllable loading ratio and release kinetics.
A class of precisely aligned flexible‐on‐rigid hybrid‐phase MOFs were synthesized by the heteroepitaxial growth of acs‐topology MOF on the surface of fcu‐topology MOF. Domain‐selective loading of multiple guests into the hybrid‐phase MOFs was achieved by size‐selective encapsulation or selective binding. A dual‐drug delivery system with controllable loading ratio and release kinetics was developed based on the hybrid‐phase MOF.
Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one of the most effective methods for cancer therapy. Nevertheless, single‐mode immunotherapy is still ...confronted with several critical challenges, such as the low immune response, the low tumor infiltration, and the complex immunosuppression tumor microenvironment. Recently, the combination of immunotherapy with other therapeutic modalities has emerged as a powerful strategy to augment the therapeutic outcome in fighting against cancer. In this review, recent research advances of the combination of immunotherapy with chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, metabolic therapy, and microwave thermotherapy are summarized. Critical challenges and future research direction of immunotherapy‐based cancer therapeutic strategy are also discussed.
Immunotherapy‐involved combination cancer therapy: the rapid development in the combination of immunotherapy with other therapeutic modalities for cancer therapy are systematically reviewed, and the critical challenges and future directions are also discussed.
To engineer patient‐derived cells into therapy‐purposed biologics is a promising solution to realize personalized treatments. Without using gene‐editing technology, a live cell‐typed therapeutic is ...engineered for tumor treatment by artificially reprogramming macrophages with hyaluronic acid‐decorated superparamagnetic iron oxide nanoparticles (HIONs). This nanoparticle‐assisted cell‐reprogramming strategy demonstrates profound advantages, due to the combined contributions from the biological regulation of HIONs and the intrinsic nature of macrophages. Firstly, the reprogrammed macrophages present a substantial improvement in their innate capabilities, such as more effective tumor targeting and more efficient generation of bioactive components (e.g., reactive oxygen species, bioactive cytokines) to suppress tumor growth. Furthermore, this cell therapeutic exhibits cytostatic/proapoptotic effects specific to cancer cells. Secondly, HIONs enable macrophages more resistant to the intratumoral immunosuppressive environment. Thirdly, the macrophages are endowed with a strong ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine‐like manner. Consequently, a synergistic tumor‐inhibition effect is achieved. This study shows that engineering nanomaterial‐reprogrammed live cells as therapeutic biologics may be a more preferable option to the commonly used approaches where nanomaterials are administrated to induce bioresponse of certain cells in vivo.
A live cell‐typed therapeutic is engineered for tumor treatment by reprogramming macrophages with HION nanoparticles. The advantage of this ex vivo cell‐reprogramming strategy is evidenced by cancer‐cell‐specific toxicity, more efficient production of bioactive components, stronger resistance against intratumoral immunosuppression, and favorable ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine‐like manner.
