Targeting Peptide Modified Platinum-based Nanomaterials And Their Application In Tumor Therapy

The development and application of intelligent Nanomaterials have provided new ideas for killing tumor cells,such as Photothermal therapy,photodynamic therapy,immunotherapy and combination therapy.In this paper,according to the different characteristics of cancer cells,a polypeptide chain that can specifically target cancer cells is designed,and two intelligent platinum nanomedicines were constructed.The research content and achievements are as follows:1.Peptide-Coated Platinum Nanoparticles for Mitochondrial Targeted NIR-Ⅱ Photothermal TherapyThermal therapy（PTT）is considered to be a substitute for traditional tumor therapy treatment,as compared with the traditional therapy,light therapy for violation of the normal tissue,especially in the near infrared area of PTT（1000-1350 nm）,because it has a deeper biological tissue penetration,lower photon scattering and higher maximum permissible exposure（1.0 W/cm²）.However,in pursuit of better therapeutic effects,a large number of near-infrared light sensitive agents have been delivered,which in turn greatly increases the damage to normal tissue cells.In this paper,we developed peptide-coated platinum nanoparticles（TPP-Pt）that can be purposely delivered to heat-sensitive mitochondria to generate sufficient temperature while causing severe damage to cancer cells with minimal side effects on normal tissue cells.Small molecule peptides targeting mitochondria give platinum nanoparticles（PtNPs）good monodispersity,high stability,and excellent biosecurity,and enhance uptake of cancer cells and mitochondrial preference,leading to effective PTT.Furthermore,in vivo studies have shown that superior tumor inhibition and negligible side effects can be achieved by prioritizing the thermosensitive mitochondrial strategy.The mitochondria-based peptide-coated platinum nanoparticles（TPP-Pt）"one-step"treatment platform demonstrated here will find great potential to overcome the challenges of low therapeutic efficiency and strong systemic side effects in PTT.2.High PTX-loading Platinum Nanoflowers for precise Photothermal and ChemotherapyPaclitaxel（PTX）is a natural and effective anti-cancer medicine.However,due to its insoluble in water and drug resistance of tumor cells,resulting in lower efficacy.The synergistic effect of photothermal and chemotherapy is considered to reduce multidrug resistance and kill tumor cell efficient.Herein,we constructed a platinum nanoflower（PtNFs）modified with RGD peptide（PtNFs-PEG-RGD）,which can specifically identifyα_Vβ₃ overexpressed on the surface of breast cancer cells.By efficiently loading the Traditional Chinese medicine PTX into the“petal”,not only can implement PTX safety and efficient delivery and release,but also the second near-infrared（NIR-Ⅱ）PTT（1000-1350nm）of PtNFs can be supplemented with PTX chemotherapy to achieve comprehensive killing of breast cancer cells（4T1）.In vitro and in vivo results proved that the efficient synergistic therapy of photothermal and chemical has obvious inhibitory effect on the heterogeneous transplanted breast cancer cell tumor model and does not cause any harm to the mouse itself.Finally,this kind of preparation with the highly effective synergistic effect of photothermal and chemotherapy has opened another window for the clinical treatment of tumors.