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Chemistry, An Asian Journal Jun 2024Designing nanomedicines with low toxicity, high targeting, excellent therapeutic effects, and precise release is always the major challenges in clinical cancer...
Designing nanomedicines with low toxicity, high targeting, excellent therapeutic effects, and precise release is always the major challenges in clinical cancer treatment. Here, we report a light-enhanced tandem-responsive nano delivery platform COF-B@X-03 for amplified anti-tumor efficiency. Biotin-loaded COF-B@X-03 could precisely target tumor cells, and the azo and hydrazone bonds in it would be depolymerized by the overexpressed azoreductase and acidic microenvironment in hypoxic tumors. In vitro experimental results indicate mitochondrial and endoplasmic reticulum stress caused by COF-B@X-03 under light is the direct cause of tumor cell death. In vivo experimental data prove COF-B@X-03 achieves low oxygen dependent phototherapy, and the maintenance of intratumoral hypoxia provides the possibility for the continuous degradation of COF-B@X-03 to generate more reactive oxygen species for tumor photodynamic therapy by released X-03. In the end, COF-B@X-03 phototherapy group achieves higher tumor inhibition rate than X-03 phototherapy group, which is 81.37%. Meanwhile, COF-B@X-03 significantly eliminates the risk of tumor metastasis. In summary, the construction of this tandem-responsive nano delivery platform provides a new direction for achieving efficient removal of solid tumors in clinical practice.
PubMed: 38924357
DOI: 10.1002/asia.202400311 -
Acta Paediatrica (Oslo, Norway : 1992) Jun 2024The most efficient emission spectrum of light for phototherapy is blue-green light emission diode light with peak emission at 478 nm. In the irradiance interval of... (Review)
Review
The most efficient emission spectrum of light for phototherapy is blue-green light emission diode light with peak emission at 478 nm. In the irradiance interval of phototherapy, the relationship between efficacy and irradiance is almost linear, and it is negatively related to the haemoglobin. The action sites of phototherapy are the extravascular compartment and cutaneous blood. The most immature neonates treated aggressively had not only a lower frequency of neurodevelopmental impairment than conservatively treated, but also greater mortality. Intermittent and continuous phototherapy are assumed to be equally efficient. Home-based fibreoptic phototherapy is effective and safe. Important progress is still occurring in phototherapy.
PubMed: 38924152
DOI: 10.1111/apa.17331 -
Chemistry, An Asian Journal Jun 2024The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe...
The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects, despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5 ± 16.52 µg mL-1; MDA-MB-231: 112.0 ± 12.31 µg mL-1; MDA-MB-231 (3D): 156.31 ± 19.35 µg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.
PubMed: 38923831
DOI: 10.1002/asia.202400616 -
Drug Design, Development and Therapy 2024Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of... (Review)
Review
Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.
Topics: Ferroptosis; Humans; Neoplasms; Antineoplastic Agents; Photochemotherapy; Animals; Small Molecule Libraries
PubMed: 38919962
DOI: 10.2147/DDDT.S472178 -
International Journal of Nanomedicine 2024Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These... (Review)
Review
Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.
Topics: Metal-Organic Frameworks; Humans; Neoplasms; Nanocomposites; Drug Delivery Systems; Animals; Photochemotherapy; Antineoplastic Agents; Nanomedicine
PubMed: 38919774
DOI: 10.2147/IJN.S463144 -
International Journal of Nanomedicine 2024This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This...
PURPOSE
This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
METHODS
Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
RESULTS
The DHTPY-Cu@ZOL exhibited proficient HO scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
CONCLUSION
Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.
Topics: Photochemotherapy; Animals; Methicillin-Resistant Staphylococcus aureus; Copper; Anti-Bacterial Agents; Photosensitizing Agents; Wound Infection; Staphylococcal Infections; Reactive Oxygen Species; Imidazoles; Pyridines; Rats; Wound Healing; Male; Humans; Rats, Sprague-Dawley
PubMed: 38919773
DOI: 10.2147/IJN.S458520 -
Journal of Nanobiotechnology Jun 2024Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of... (Review)
Review
Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.
Topics: Humans; Breast Neoplasms; Female; Nanostructures; Nanoparticles; Animals; Photochemotherapy; Inorganic Chemicals
PubMed: 38918821
DOI: 10.1186/s12951-024-02644-9 -
Asian Pacific Journal of Cancer... Jun 2024Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor...
OBJECTIVE
Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities.
METHODS
In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient.
RESULTS
Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF.
CONCLUSION
This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.
Topics: Humans; Photochemotherapy; NF-kappa B; Photosensitizing Agents; Aminolevulinic Acid; Female; Cell Proliferation; Breast Neoplasms; Dimethyl Fumarate; Apoptosis; Reactive Oxygen Species; Tumor Cells, Cultured; Cell Line, Tumor
PubMed: 38918667
DOI: 10.31557/APJCP.2024.25.6.2051 -
ACS Applied Materials & Interfaces Jun 2024Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an...
Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal-organic framework (MOF)-derived titanium oxide nanoparticle (MCT NP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing "immunogenic cell death" (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. / results demonstrate that MCT NPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCT NPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)' infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCT NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.
PubMed: 38917296
DOI: 10.1021/acsami.4c04985 -
ACS Biomaterials Science & Engineering Jun 2024This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs...
This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs exhibit notable features, including potential bioelimination through renal clearance and efficient photothermal conversion in the near-infrared region with multicolor photoluminescence across the visible spectrum. Our research demonstrates high biocompatibility and effective near-infrared (NIR)-triggered photothermal toxicity when targeting mammospheres and patient-derived tumor organoids. Moreover, the study delves into the intricate cellular responses induced by CD-mediated hyperthermia. This involves efficient tumor mass death, activation of the p38-mitogen-activated protein kinase (MAPK) pathway, and upregulation of genes associated with apoptosis, hypoxia, and autophagy. The interaction of CDs with mammospheres reveals their ability to penetrate the complex microenvironment, impeded at 4 °C, indicating an energy-dependent endocytosis mechanism. This observation underscores the CDs' potential for targeted drug delivery, particularly in anticancer therapeutics. This investigation contributes to understanding the multifunctional properties of sulfur-doped CDs and highlights their promising applications in cancer therapeutics. Utilizing 3-D tumor-in-a-dish patients' organoids enhances translational potential, providing a clinically relevant platform for assessing therapeutic efficacy in a context mirroring the physiological conditions of cancerous tissues.
PubMed: 38916153
DOI: 10.1021/acsbiomaterials.4c00209