Nanoparticles Based On Zinc Phthalocyanine For Combined Antitumor/Antibacterial Therapy

Pathogenic bacterial infections and malignancies have been major diseases threatening human health,and in recent years many emerging therapeutic approaches have shown great potential in the anti-tumor/anti-bacterial field.Photodynamic therapy is becoming a very promising new therapy due to its non-resistance,low side effects and spatio-temporal selectivity,but it is difficult to achieve the desired therapeutic effect with a single treatment modality.Combining photodynamic therapy with other therapies to achieve synergistic therapeutic effects has become a new direction of research.In this study,two different nanoparticles based on zinc phthalocyanine were constructed for combined antibacterial and antitumour therapy,respectively.Firstly,in this study,the photosensitizer zinc phthalocyanine was assembled with polymyxin B into nanoparticles Zn Pc（COOH）₈:PMB for the combination of photodynamic therapy and antibiotics.The nanoparticles have good stability and can specifically bind to Gram-negative bacteria to achieve drug release,and compared with free Zn Pc（COOH）₈ and PMB,Zn Pc（COOH）₈:PMB had stronger photodynamic and antibacterial activities against Gram-negative bacteria and exerted synergistic antibacterial effects by disrupting the bacterial outer membrane to promote drug uptake and accelerate bacterial death.The antibacterial activity evaluation in vivo showed that Zn Pc（COOH）₈:PMB had stronger antibacterial activity against E.coli and had a significant effect on accelerating wound healing of infections.It is worth mentioning that the fluorescence property of Zn Pc（COOH）₈ also allowed Zn Pc（COOH）₈:PMB to have a significant detection effect against Gram-negative bacteria.Moreover,due to its specificity against Gram-negative bacteria,Zn Pc（COOH）₈:PMB nanoparticles exhibit better biocompatibility by exerting a synergistic antibacterial effect while reducing the toxic side effects of polymyxin B.The construction principle and combined antibacterial strategy of the nanoparticles in this study can be applied to other photosensitizers and antibiotics for bacterial detection and treatment of wound infections.Secondly,in this study,a new nanoparticle Zn Pc（COOH）₄-Fe was synthesized through the assembly of photosensitizer zinc phthalocyanine and Fe³⁺,and loaded with the chemotherapeutic drug doxorubicin for the combined application of photodynamic therapy and chemotherapeutic methods.Zn Pc（COOH）₄-Fe:DOX not only achieved the loading of DOX,but also had good stability.Both Zn Pc（COOH）₄-Fe and Zn Pc（COOH）₄-Fe:DOX have good fluorescence properties and ROS generation ability,and can exhibit excellent photodynamic activity.Zn Pc（COOH）₄-Fe:DOX exhibited stronger cytotoxicity and exerted synergistic antitumor activity.Zn Pc（COOH）₄-Fe nanoparticles can also be used for the loading of other antitumor drugs,providing a new avenue for the combination therapy of antitumor.