1. Layer-by-Layer Nanoparticles for Calcium Overload in situ Enhanced Reactive Oxygen Oncotherapy.
- Author
-
Zhang B, Man J, Guo L, Ru X, Zhang C, Liu W, Li L, Ma S, Guo L, Wang H, Wang B, Diao H, Che R, and Yan L
- Subjects
- Humans, Animals, HeLa Cells, Reactive Oxygen Species metabolism, Mice, Hyaluronic Acid chemistry, Porphyrins chemistry, Porphyrins pharmacology, Porphyrins pharmacokinetics, Porphyrins administration & dosage, Photothermal Therapy methods, Hydrogen-Ion Concentration, Ultrasonic Therapy methods, Neoplasms therapy, Neoplasms drug therapy, Mitochondria drug effects, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Mice, Inbred BALB C, Mice, Nude, Layer-by-Layer Nanoparticles, Nanoparticles chemistry, Calcium chemistry, Calcium Carbonate chemistry, Calcium Carbonate pharmacology, Tumor Microenvironment drug effects
- Abstract
Background: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME)., Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH-responsive CaCO
3 , targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+ , with TAPP generating1 O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2 O2 and also exhibited a strong PTT effect., Results: CuS@TAPP-CaCO3 /HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy., Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications., Competing Interests: The authors declare no competing interest in this work., (© 2024 Zhang et al.)- Published
- 2024
- Full Text
- View/download PDF