In recent years, conventional treatments including surgery, chemotherapy and radiotherapy have been the main approaches in tumour therapy. Cancer immunotherapy is a new therapeutic modality to fight ...cancer by harnessing the power of patients' own immune system. Ongoing research related to these therapies has demonstrated their advantages and intrinsic limitations. Nanomaterial-based platforms are utilized in these emerging fields. In particular, a combination of other treatment methods with cancer immunotherapy to achieve precision medicine and prevent recurrence and metastasis, could improve patients' outcome. The combined multiple treatments have superior efficacy to any monotherapy alone in producing improved anti-cancer activity. Therefore, it's necessary to summarise research advances in nanomaterial-based combination cancer immunotherapy contributing to clinical transformation. This review is based on the principles of cancer immunotherapy and the combined treatment design reflected by advances in materials science, including the structures of nanoplatforms and their underlying mechanisms towards cancer. The ultimate goals are to stimulate the design of better strategies for versatile use in the future based on biomaterial engineering methods to enhance the efficacy of combined cancer treatments, and to provide new ideas for the prospects of a synergistic cancer combination immunotherapy for clinical application transformation.
This review aims to summarize various synergistic combination cancer immunotherapy strategies based on nanomaterials.
Abstract
In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that ...exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe
3+
) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.
The synthesis (by a facile two‐step sol–gel process), characterization, and application in controlled drug release is reported for monodisperse core–shell‐structured Fe3O4@nSiO2@mSiO2@NaYF4: Yb3+, ...Er3+/Tm3+ nanocomposites with mesoporous, up‐conversion luminescent, and magnetic properties. The nanocomposites show typical ordered mesoporous characteristics and a monodisperse spherical morphology with narrow size distribution (around 80 nm). In addition, they exhibit high magnetization (38.0 emu g−1, thus it is possible for drug targeting under a foreign magnetic field) and unique up‐conversion emission (green for Yb3+/Er3+ and blue for Yb3+/Tm3+) under 980 nm laser excitation even after loading with drug molecules. Drug release tests suggest that the multifunctional nanocomposites have a controlled drug release property. Interestingly, the up‐conversion emission intensity of the multifunctional carrier increases with the released amount of model drug, thus allowing the release process to be monitored and tracked by the change of photoluminescence intensity. This composite can act as a multifunctional drug carrier system, which can realize the targeting and monitoring of drugs simultaneously.
A multifunctional material (mesoporous, magnetic, and up‐conversion luminescent) is prepared through a novel two‐step sol–gel process. The materials show ordered mesopores, high magnetization values, and up‐conversion luminescence. This product is used as a drug delivery system, which can be monitored or tracked based on their magnetic and up‐conversion luminescent features.
The organized assembly of particles into superstructures is typically governed by specific molecular interactions or external directing factors associated with the particle building blocks, both of ...which are particle-dependent. These superstructures are of interest to a variety of fields because of their distinct mechanical, electronic, magnetic and optical properties. Here, we establish a facile route to a diverse range of superstructures based on the polyphenol surface-functionalization of micro- and nanoparticles, nanowires, nanosheets, nanocubes and even cells. This strategy can be used to access a large number of modularly assembled superstructures, including core-satellite, hollow and hierarchically organized supraparticles. Colloidal-probe atomic force microscopy and molecular dynamics simulations provide detailed insights into the role of surface functionalization and how this facilitates superstructure construction. Our work provides a platform for the rapid generation of superstructured assemblies across a wide range of length scales, from nanometres to centimetres.
The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not ...enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au25(Capt)18−(Au25) are assembled into the mesoporous silica shell coating outside of Nd3+‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au25 shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd3+ and Yb3+ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.
Au nanoclusters with photodynamic therapy and photothermal therapy effects are combined with upconversion nanoparticles for the first time to form a new multifunctional cancer therapy platform with multimode imaging and dual phototherapy function. The nanoparticles could be promising to achieve the light‐induced and imaging‐guided cancer therapy with low side effects.
Controlling anticancer drug activity and release on demand is very significant in cancer therapy. The photoactivated platinum(IV) pro-drug is stable in the dark and can be activated by UV light. In ...this study, we develop a multifunctional drug delivery system combining upconversion luminescence/magnetic resonance/computer tomography trimodality imaging and NIR-activated platinum pro-drug delivery. We use the core–shell structured upconversion nanoparticles to convert the absorbed NIR light into UV to activate the trans-platinum(IV) pro-drug, trans,trans,trans-Pt(N3)2(NH3)(py)(O2CCH2CH2COOH)2. Compared with using the UV directly, the NIR has a higher tissue penetration depth and is less harmful to health. Meanwhile, the upconversion nanoparticles can effectively deliver the platinum(IV) pro-drugs into the cells by endocytosis. The mice treated with pro-drug-conjugated nanoparticles under near-infrared (NIR) irradiation demonstrated better inhibition of tumor growth than that under direct UV irradiation. This multifunctional nanocomposite could be used as multimodality bioimaging contrast agents and transducers by converting NIR light into UV for control of drug activity in practical cancer therapy.
Cancer immunotherapies, particularly therapeutic vaccination, do not typically generate robust anti-tumour immune responses. Here, we show that the intratumoral burst release of the protein annexin ...A5 from intravenously injected hollow mesoporous nanoparticles made of diselenide-bridged organosilica generates robust anti-tumour immunity by exploiting the capacity of primary tumours to act as antigen depots. Annexin A5 blocks immunosuppressive apoptosis and promotes immunostimulatory secondary necrosis by binding to the phagocytic marker phosphatidylserine on dying tumour cells. In mice bearing large established tumours, the burst release of annexin A5 owing to diselenide-bond cleavage under the oxidizing conditions of the tumour microenvironment and the reducing intracellular conditions of tumour cells induced systemic cytotoxic T-cell responses and immunological memory associated with tumour regression and the prevention of relapse, and led to complete tumour eradication in about 50% of mice with orthotopic breast tumours. Reducing apoptosis signalling via in situ vaccination could be a versatile strategy for the generation of adaptive anti-tumour immune responses.
Among various novel antimicrobial therapies, sonodynamic therapy (SDT) exhibits its advantages for the treatment of bacterial infections due to its high penetration depth and low side effects. In ...this study, a new nanosonosensitizer (HFH@ZIF-8) that loads sonosensitizer hematoporphyrin monomethyl ether (HMME) into zeolitic imidazolate framework-8 (ZIF-8), was constructed for killing multidrug-resistant (MDR) bacteria and treatment of in vivo infection diseases by SDT. In particular, the developed HFH@ZIF-8 exhibited enhanced water-solubility, good biocompatibility, and improved disease-targeting capability for delivering and releasing HMME and ablating the infected lesion. More importantly, the presence of oxygen-carrying hemoglobin for HFH@ZIF-8 can offer sufficient oxygen consumption by SDT, augmenting the efficacy of SDT by improving ROS generating efficiency against deep tissue multidrug-resistant bacterial infection. Therefore, this study paves a new avenue for treating infection disease, particularly for antibiotic resistant bacterial infection.
Abstract
Tumor surgical resection is the major strategy for cancer treatment. Meanwhile, perioperative treatment especially the postoperative adjuvant anticancer strategies play essential roles in ...satisfying therapeutic results and rapid recovery. Postoperative tumor recurrence, metastasis, bleeding, inter‐tissue adhesion, infection, and delayed wound healing are vital risks that could lead to poor prognosis or even treatment failure. Therefore, methods targeting these postoperative complications are in desperate need. In situ biomaterial‐based drug delivery platforms are promising candidates for postoperative treatment and recovery, resulting from their excellent properties including good biocompatibility, adaptive shape, limited systemic effect, designable function, and easy drug loading. In this review, we focus on introducing the gel/hydrogel‐based in situ biomaterial platforms involving their properties, advantages, and synthesis procedures. Based on the loaded contents in the gel/hydrogel such as anticancer drugs, immunologic agents, cell components, and multifunctional nanoparticles, we further discuss the applications of the in situ platforms for postoperative tumor recurrence and metastasis inhibition. Finally, other functions aiming at fast postoperative recovery were introduced, including hemostasis, antibacterial infection, adhesion prevention, tissue repair, and wound healing. In conclusion, gel/hydrogel is a developing and promising platform for postoperative treatment, exhibiting gratifying therapeutic effects and inconspicuous toxicity to normal tissues, which deserves further research and exploration.
In this study, we report a new controlled release system based on up-conversion luminescent microspheres of NaYF4:Yb3+/Er3+ coated with the smart hydrogel poly(N-isopropylacrylamide)-co-(methacrylic ...acid) (P(NIPAM-co-MAA)) (prepared using 5 mol % of MAA) shell. The hybrid microspheres show bright up-conversion fluorescence under 980 nm laser excitation, and turbidity measurements show that the low critical solution temperature of the polymer shell is thermo- and pH-dependent. We have exploited the hybrid microspheres as carriers for Doxorubicin hydrochloride (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is pH-triggered thermally sensitive. Changing the pH to mildly acidic condition at physiological temperature deforms the structure of the shell, causing the release of a large number of DOX from the microspheres. The drug-loaded microspheres exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells. The endocytosis process of drug-loaded microspheres is observed using confocal laser scanning microscopy and up-conversion luminescence microscopy. Meanwhile, the as-prepared NaYF4:Yb3+/Er3+@SiO2@P(NIPAM-co-MAA) microspheres can be used as a luminescent probe for cell imaging. In addition, the extent of drug release can be monitored by the change of up-conversion emission intensity. These pH-induced thermally controlled drug release systems have potential to be used for in vivo bioimaging and cancer therapy by the pH of the microenvironment changing from 7.4 (normal physiological environment) to acidic microenvironments (such as endosome and lysosome compartments) owing to endocytosis.
PDF
