Localization of Cancer Cells for Subsequent Robust Photodynamic Therapy by ROS Responsive Polymeric Nanoparticles With Anti‐Metastasis Complexes NAMI‐A

Abstract

Photodynamic therapy (PDT), as a new type of light‐mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non‐resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen‐dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed. Herein, a near‐infrared light‐activated photosensitive polymer is synthesized and branched the anti‐metastatic ruthenium complex NAMI‐A on the side, which is further assembled to form nanoparticles (NP2) for breast cancer therapy. NP2 can kill tumor cells by generating ROS under 808 nm radiation (NP2 + L), reduce the expression of matrix metalloproteinases (MMP2/9) in cancer cells, decrease the invasive and migration capacity of cancer cells, and eliminate cancer cells. Further animal experiments show that NP2 + L can inhibit tumor growth and reduce liver and lung metastases. In addition, NP2 + L can activate the immune system in mice to avoid tumor recurrence. In conclusion, a PDT capable of both preventing tumor metastasis and precisely hitting the primary tumor to achieve effective treatment of highly metastatic cancers is developed.

Polymeric Nanoparticles Containing Ruthenium Complexes for Biomedical Applications: A Mini-Review on Recent Developments

“…Contrary to the example reported just above, the triblock copolymer is fully synthesized and then functionalized with a Ru complex to afford a polymer covalently linked to NAMI-A (Figure ). To do so, a rigid hydrophobic and light-sensitive block is chain-extended on its two alcohol arms to add a reactive oxygen species (ROS)-sensitive unit (via a disulfide bond) containing alcohol moieties using a dianhydride before a methoxypoly(ethylene glycol) is added to cap both hydrophobic arms. This reaction allows for two carboxylic acid groups to be released and which are subsequently reacted with histamine via amidation coupling with N -hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC).…”

Nanomedomics

“…A variety of nanomaterials are typically used to deliver bioactive molecules and living bio-organisms to form nanomedicines through physical encapsulation, electrostatic interactions, and chemical conjugation. In addition, intratumor endogenous stimuli (pH, − enzyme, − redox ,− ), as well as exogenous stimuli (light, − electricity, , sound, − magnetism, − heat − ), can be applied to trigger the breakdown of sophisticated chemical bonds and/or physical structures of drug carriers to release the active ingredients. Therefore, it is generally assumed that once the nanomedicines enter cancer cells, the active anticancer agents could be released to exert the anticancer effect.…”

Bright and White Light-Triggered Aggregation-Induced Emission Nanoparticles Prepared in Miniemulsions for Photodynamic Theranostics

“…Photodynamic therapy (PDT) excited by visible light or near-infrared light has been widely applied for cancer treatments, taking advantage of its high spatiotemporal precision, noninvasiveness, and low multidrug resistance. − Photosensitizers (PSs), as the cornerstone of PDT, are photoexcited to the singlet excited state (S 1 ), generating S 1 excitons, transiting to the triplet excited state (T 1 ) via the intersystem crossing (ISC) process, and undergoing type I (electron transfer) or type II (energy transfer) photochemical paths to produce highly cytotoxic reactive oxygen species (ROS), including hydroxyl radicals (HO·), superoxide radicals (O 2 •– ), and singlet oxygen ( 1 O 2 ), for destruction of targeted cells or tissues. − In contrast to traditional aggregation-caused quenching (ACQ) PSs, aggregation-induced emission (AIE) PSs hold stronger ability to generate ROS in the concentrated or confined environments, thanks to the suppressed nonradiative pathway. − More promisingly, simultaneously emitting fluorescence and producing ROS make AIE PSs capable of fluorescence imaging-guided PDT, thereafter visualizing the position of drugs and tumors and performing noninterventional treatments with high spatial and temporal precision. − …”