Photosensitizer-Loaded Multifunctional Chitosan Nanoparticles for Simultaneous in Situ Imaging, Highly Efficient Bacterial Biofilm Eradication, and Tumor Ablation

Abstract

In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC−MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm 2 for 5 min, the CMC−MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC−MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC−MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.

Polysaccharide-Based Formulations for Healing of Skin-Related Wound Infections: Lessons from Animal Models and Clinical Trials

“…The treatment with PDT plus CMCNPs showed high efficiency in managing bacterial infection when compared with the other experimental groups (animals treated with laser, CMCNPs or untreated). The rabbits treated with PDT plus CMCNPs also showed marked reductions on TNF-α and IL-6 levels and greater resolution of the wound in relation to other groups [70].…”

Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework‐Based Drug Delivery Systems

“…In Vitro Antibacterial Test—Bactericidal Activity: S. aureus , E. coli , or MRSA (100 µL, 1 × 10 4 CFU mL −1 ) were added to tubes (1 mL, 1 × 10 4 CFU mL −1 ) for different treatments, i.e., no treatment, ZPM NPs, ZPMA NPs, ZPMAVP NPs only or combined with laser irradiation. According to the previous work, the irradiated intensity and irradiation time were set to 202 mW cm −2 and 5 min at 630 nm. The changes of bacteria numbers were determined by agar plate counting method.…”

“…Although the incidence of endophthalmitis in the developed countries is not high (between 0.07% and 0.13%) after IOL implantation in cataract extraction surgery, the situation is serious in the developing countries . Once endophthalmitis happens, it is commonly treated through injections of antibiotics directly into the vitreous cavity 10b,14. Successful inhibition of infectious endophthalmitis greatly depends on timely diagnosis and rapid appropriate therapy, while it will be difficult to eliminate endophthalmitis once it occurs and clinically antibiotics can only be used to control the disease development.…”

“…On the other hand, nanoparticles (NPs) such as metal–organic frameworks (MOFs) in nanoscale with a high drug‐loading capacity can be designed and modified for targeting and local delivery of antibacterial agents . Furthermore, NPs need to be coated with immune evasion molecules such as polyethylene glycol (PEG) to avoid being swallowed by the body's metabolic organs and being recognized and removed by macrophages in vivo 8a,14…”

Leveraging metal oxide nanoparticles for bacteria tracing and eradicating

“…51,52 Owing to nonspecific action mechanism and low mutagenic potential, ROS have been shown to be highly cytotoxic for virtually all microorganisms with no resistance concern. 53,54 It is noted that the production of ROS by metal oxide nanoparticles mainly relies on endogenous reactions and exogenous physical excitation ( Figure 2), 55 which is originally considered as the basic classification profile in the following discussion.…”