The synthesis and application of nano doxorubicin-indocyanine green matrix metalloproteinase-responsive hydrogel in chemophototherapy for head and neck squamous cell carcinoma
Abstract:BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study… Show more
“…In another construction, DOX was covalently linked with a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH 2 (AHNP) to form an MMP-2 sensitive nanoconjugate for synergistic chemotherapy and biotherapy of HER2-positive breast cancer 65 . Apart from these, DOX-based nanoscale multidrug systems have also been developed to enable coordinated treatment of cancer, such as chemophototherapy 66 , 67 . Figure 1 Schematic illustration of MMP-2-responsive dePEGylation and RGD-enhanced endocytosis of DOX-carried block copolymer micelles for targeted drug delivery and cell killing.…”
Section: Protease-responsive Nanodds For the Targeted Theranostics Of Malignancymentioning
Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.
“…In another construction, DOX was covalently linked with a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH 2 (AHNP) to form an MMP-2 sensitive nanoconjugate for synergistic chemotherapy and biotherapy of HER2-positive breast cancer 65 . Apart from these, DOX-based nanoscale multidrug systems have also been developed to enable coordinated treatment of cancer, such as chemophototherapy 66 , 67 . Figure 1 Schematic illustration of MMP-2-responsive dePEGylation and RGD-enhanced endocytosis of DOX-carried block copolymer micelles for targeted drug delivery and cell killing.…”
Section: Protease-responsive Nanodds For the Targeted Theranostics Of Malignancymentioning
Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.
“…Enzymatic-responsive hydrogels, with synergistic photodynamic (ICG) and chemotherapeutic (DOX) mechanisms of action exhibiting enhanced activity, were recently reported for head and neck cancer. Nanoparticles containing ICG or DOX were incorporated in hyaluronic acid-acrylate-based hydrogels, which were further conjugated to MMP [ 222 ]. Mice bearing SCC-15 tumors submitted to intratumoral injection of the developed multifunctional hydrogel exhibited strong tumor regression that was significantly higher than the one attained with hydrogels containing only ICG or DOX.…”
Section: Ligand-targeted Nanocarriers For the Delivery Of Photosenmentioning
Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers.
“…Combined therapy is relatively more popular than monotherapy because it can yield the greatest returns on investment. Wang et al 149 synthesized a novel nano DOX‐ICG (Indocyanine green) MMP‐responsive hydrogel (NDIMH) for anticancer study. The MMPs‐responsive property and ICG‐based FL imaging enhanced the accuracy of hydrogel implantation.…”
Section: The Application Of Hydrogels In Localized Tumor Treatmentmentioning
Due to limitations of treatment and the stubbornness of infiltrative tumor cells, the outcome of conventional antitumor treatment is often compromised by a variety of factors, including severe side effects, unexpected recurrence, and massive tissue loss during the treatment. Hydrogel‐based therapy is becoming a promising option of cancer treatment, because of its controllability, biocompatibility, high drug loading, prolonged drug release, and specific stimuli‐sensitivity. Hydrogel‐based therapy has good malleability and can reach some areas that cannot be easily touched by surgeons. Furthermore, hydrogel can be used not only as a carrier for tumor treatment agents, but also as a scaffold for tissue repair. In this review, we presented the latest researches in hydrogel applications of localized tumor therapy and highlighted the recent progress of hydrogel‐based therapy in preventing postoperative tumor recurrence and improving tissue repair, thus proposing a new trend of hydrogel‐based technology in localized tumor therapy. And this review aims to provide a novel reference and inspire thoughts for a more accurate and individualized cancer treatment.
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