Declaration of competing interest
The authors report no declarations of interest.
This research was supported, in part or in whole, by the National Natural Science Foundation of China (Nos. 81471785, 81671821, 11772088, 11802056, 31800780, 11972111, 31900940, U19A2006, 32071304), the Basic Research Program of Sichuan Science and Technology (Nos. 2021YJ0130, 2019YJ0183, 2019YJ0184), China Postdoctoral Science Foundation (Nos. 2018M640904, 2019T120831), and the Fundamental Research Funds for the Central Universities (No. ZYGX2019J117).
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Treatment of Alzheimer's disease with small-molecule photosensitizers
2023, Chinese Chemical Letters
Alzheimer's disease is a neurodegenerative disease that signals for excess β-amyloid (Aβ) aggregation. Although people have made great attempts to control the aggregation of Aβ, no effective medications have been produced yet. Due to its excellent temporal and spatial selectivity, photodynamic treatment has been gradually employed and interfered in the aggregation process of Aβ, with some achievement. To enhance the research and application of photodynamic therapy in Alzheimer's disease, this paper reviews the progress of small-molecule photosensitizers in the treatment of Alzheimer's disease in recent years and outlines existing tactics and potential obstacles.
A type I AIE photosensitiser-loaded biomimetic nanosystem allowing precise depletion of cancer stem cells and prevention of cancer recurrence after radiotherapy
Radioresistance of Cancer stem cell (CSC) is an important cause of tumor recurrence after radiotherapy (RT). Herein, we designed a type I aggregation-induced emission (AIE) photosensitiser-loaded biomimetic mesoporous organosilicon nanosystem (PMT) for precise depletion of CSC to prevent tumor recurrence after RT. This PMT system is composed of a type I AIE photosensitiser (TBP-2) loaded mesoporous organosilicon nanoparticles (MON) with an outer platelet membrane. The PMT system is able to specifically target CSC. Intracellular glutathione activity leads to MON degradation and the release of TBP-2. Type I photodynamic therapy is activated by exposure to white light, producing a large amount of hydroxyl radicals to promote CSC death. The results of in vivo experiments demonstrated specific removal of CSC following PMT treatment, with no tumor recurrence observed when combined with RT. However, tumor recurrence was observed in mice that received RT only. The expression of CSC markers was significantly reduced following PMT treatment. We demonstrate the development of a system for the precise removal of CSC with good biosafety and high potential for clinical translation. We believe the PMT nanosystem represents a novel idea in the prevention of tumor recurrence.
Iridium photosensitizer constructed liposomes with hypoxia-activated prodrug to destrust hepatocellular carcinoma
2023, Chinese Chemical Letters
Hypoxic tumor microenvironment is a major challenge for photodynamic therapy (PDT). To overcome this problem, PDT combined hypoxia-activated chemotherapy is a promising strategy for hypoxic cancer therapy. Herein, a multifunctional liposome (AQ4N-Ir1-sorafenib-liposome) is prepared by encapsulating a hypoxia-activated prodrug AQ4N, a photosensitizer iridium(III) complex and hepatocellular carcinoma (HCC) targeting drug sorafenib, for synergistic therapy of HCC. Ir1-mediated PDT upon irradiation induces ROS generation and hypoxic environment, which leads to the disassembly of the liposome and activates the antitumor activity of AQ4N. Meantime, the co-delivered sorafenib could effectively target therapy of HCC. It is noted that ferroptosis mechanism is proved during the treatment. This work contributes to the design of hypoxia-responsive multifunctional liposome for combination of chemotherapy, targeting therapy and PDT. It is a promising strategy for hypoxic HCC therapy.
Fabrication of doxorubicin loaded aptamer-functionalized cationic β-lactoglobulin nanocomplex: A biocompatible multifunctional nanoplatform for encapsulation and controlled release of anticancer drugs
2023, Journal of Drug Delivery Science and Technology
Owing to elegant biomacromolecule features, proteins have been investigated to prepare a multifunctional and targeted nanoscale drug delivery systems. In this work, a novel cationic protein based nanocarrier, AS1411 aptamer-conjugated poly-l-lysine/β-lactogolubolin nanoparticles (BNP/PLL/Apt), was fabricated. The as-prepared nanocarrier offers an innovative formulation that combines the outstanding properties of protein nanocarriers and aptamer as a targeting agent for chemotherapy. To demonstrate the therapeutic potential of BNP/PLL/Apt, the nanocarriers were loaded with doxorubicin (DOX). The DOX-loaded BNP/PLL/Apt ([emailprotected]/PLL/Apt) exhibited high drug encapsulation efficiency, as high as 92%, and the controlled drug release profile in a mildly acidic physiological condition that could enhance therapeutic efficiency in cancerous cells. The in vitro assays of [emailprotected]/PLL/Apt illustrated that the synthesized drug delivery system was hemocompatible based on hemagglutination, coagulation and complement activation assay results. Besides, [emailprotected]/PLL/Apt was more potent against MCF-7 tumor cells than the free DOX. Thanks to the particular recognition between AS1411 aptamer and its receptor over-expressed on cancer cells, the BNP/PLL/Apt NPs show the enhanced cellular uptake in MCF-7cells compared with the BNPs without aptameric modification. Moreover, the computational studies exhibited the reasonable binding affinity of β-lactogolubolin to DOX and activity of AS1411 aptamer against cancer cells which confirmed the experimental results. Overall, the resultants of this research possessed numerous advantages of [emailprotected]/PLL/Apt over free chemotherapy drugs and confirmed its great potential to address the clinical challenges observed in targeted anticancer drug delivery system.
A tumor microenvironment-responsive core-shell tecto dendrimer nanoplatform for magnetic resonance imaging-guided and cuproptosis-promoted chemo-chemodynamic therapy
2023, Acta Biomaterialia
Theranostic nanoplatforms for combination tumor therapy have gained lots of attention recently due to the optimized therapeutic efficiency and simultaneous diagnosis performance. Herein, a novel tumor microenvironment (TME)-responsive core-shell tecto dendrimer (CSTD) was assembled by phenylboronic acid- and mannose-modified poly(amidoamine) dendrimers via the phenylboronic ester bonds that are responsive to low pH and reactive oxygen species (ROS), and efficiently loaded with copper ions and chemotherapeutic drug disulfiram (DSF) for tumor-targeted magnetic resonance (MR) imaging and cuproptosis-promoted chemo-chemodynamic therapy. The formed CSTD-Cu(II)@DSF could be specifically taken up by MCF-7 breast cancer cells, accumulated to the tumor model after circulation, and released drugs in response to the weakly acidic TME with overexpressed ROS. The enriched intracellular Cu(II) ions could induce the oligomerization of lipoylated proteins and proteotoxic stress for cuproptosis, and lipid peroxidation for chemodynamic therapy as well. Moreover, the CSTD-Cu(II)@DSF could cause the dysfunction of mitochondria and arrest the cell cycle at the G2/M phase, leading to enhanced DSF-mediated cell apoptosis. As a result, CSTD-Cu(II)@DSF could effectively inhibit the growth of MCF-7 tumors by a combination therapy strategy integrating chemotherapy with cuproptosis and chemodynamic therapy. Lastly, the CSTD-Cu(II)@DSF also displays Cu(II)-associated r1 relaxivity, allowing for T1-weighted real-time MR imaging of tumors in vivo. The developed tumor-targeted and TME-responsive CSTD-based nanomedicine formulation may be developed for accurate diagnosis and synergistic treatment of other cancer types.
Constructing an effective nanoplatform for the combination of therapeutic effects and real-time tumor imaging remains a challenge. In this study, we reported for the first time an all-in-one tumor-targeted and tumor microenvironment (TME) responsive nanoplatform based on core-shell tecto dendrimer (CSTD) for the cuproptosis-promoted chemo-chemodynamic therapy and enhanced MR imaging. The efficient loading, selective tumor-targeting, and TME-responsive release of Cu(II) and disulfiram could enhance the intracellular accumulation of drugs, induce cuproptosis of cancer cells, and amplify the synergistic chemo-chemodynamic therapeutic effect, resulting in enhanced MR imaging and accelerated tumor eradication. This study sheds new light on the development of theranostic nanoplatforms for early accurate diagnosis and effective treatment of cancers.
Emerging Prodrug-Engineered nanomedicines for synergistic Chemo-Phototherapy
2022, Chemical Engineering Journal
Citation Excerpt :
Moreover, large amount of reduced Mn2+ could also be further employed as T1- and T2-weighted contrast agents for MRI . Tumor hypoxia is a common phenomenon in solid tumors, which could be mainly attributed to the rapid proliferation, aberrant blood vessels and insufficient blood supply [102-104]. Rational design of hypoxia-activated prodrugs (HAPs) has become a research hotpot in cancer therapy.
Chemotherapy is one of the most commonly used treatment regimens for malignant tumors. However, the clinical outcomes of chemotherapy alone are still far from satisfactory, due to the insufficient therapeutic effect and serious side effects. Chemo-phototherapy, with the excellent advantages of synergetic treatment effect and dosage reduction of chemotherapeutics, has received wide attention in multimodal cancer therapy. Prodrug-engineered nanosystems, integrating prodrug strategy with biomedical nanotechnology, offer many benefits for efficient combination drug delivery. In recent years, a wide variety of prodrug-engineered nanomedicines have been developed for efficient chemo-phototherapy. In this review, we intend to outline the latest trends in this field, with a special focus on polymeric prodrug-nanosystems, prodrug/drug co-encapsulation nanocarriers and small-molecule prodrug-nanoassemblies. This review highlights the design rationale, advantages and challenges of the emerging prodrug-engineered nanomedicines in synergistic chemo-phototherapy.
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© 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.