6.5.5 The application of polymer nano-drug carrier...
Phototherapy is a highly effective and accurate cancer therapy.Phototherapy mainly includes photothermal therapy and photodynamic therapy.Photothermal therapy is to use the photothermal effect of polymer nano-drug carriers or the encapsulated drugs to transform the absorbed light energy into heat energy，so as to improve the local temperature of tumor tissues to eliminate tumors.To meet the requirements of deeper penetration and low damage to normal tissue，the NIR Ⅰ （750-1000 nm）or Ⅱ（1000-1350 nm）lasers with less tissue absorption are usually selected as the light source.To realize the photothermal tumor treatment，the construction of polymer nano-drug carriers requires conjugation or loading small molecules，inorganic nanomaterials with photothermal conversion effect，or using semiconductor polymers as the carrier materials.For example，Wang et al.prepared nanobubbles with PEG-b-PLGA by double emulsion method（Figure 6-10（b）），which contained perfluoropentane and IR780 in the core and membrane of the nano-spheres，respectively.Among them，IR780 is a hydrophobic small molecule photothermal conversion agent，and perfluoropentane is a low boiling point（29℃）liquid.During photothermal treatment，perfluoropentane is heated and vaporized rapidly，thus transforming the nanobubbles into microbubbles.The enlarged nanobubbles can not only enhance the signal intensity of melanoma ultrasound imaging，but also improve the vascular permeability，so that more nanobubbles can enter the tumor and enhance the photothermal treatment effect.In addition to improving the tumor enrichment effect of polymer nano-drug carriers，improving the photothermal conversion efficiency of polymer nano-drug carriers，designing and utilizing laser with deeper penetration depth，and controlling the damage of photothermal therapy to normal tissues are all the directions that need to be explored in the photothermal tumor therapy of polymer nano-drug carriers.The biggest problem of photothermal therapy is the limited penetration depth of laser，which is only a few millimeters.It can only be used to treat melanoma in the superficial skin，and it is difficult to achieve the treatment of tumors in deep tissues.The development of combination therapy of photothermal therapy with chemotherapy，immunotherapy，surgery，and radiotherapy is one of the potential methods to solve the bottleneck problem of photothermal therapy.
Tumor photodynamic therapy refers to a cancer treatment method that uses polymer nano-drug carriers enriched at the tumors to generate reactive oxygen species under laser irradiation and kill tumor cells.The production of reactive oxygen species inside cells can promote cells to produce oxidative stress environment and damage biological macromolecules such as DNA and protein，eventually leading to the death of tumor cells.To realize tumor photodynamic therapy，it is necessary to conjugate or load photosensitizers in polymer nanodrug carriers.When the photosensitizers are excited by a laser，it can generate singlet oxygen through the energy transfer（type Ⅱ）pathway or free radicals through the electron transfer（type Ⅰ）pathway.The type Ⅱ pathway requires oxygen consumption.On the one hand，in view of the hypoxic microenvironment within the tumor，how to provide more oxygen sources is one of the key issues that need to be addressed for type Ⅱ photodynamic therapy.Pokorski et al.prepared polymer micelles using fluoropolymers of poly（TFEMAco-OEGMEMA）with terminal cationic zinc-ethyl phenyl porphyrin，in which cationic zincethyl phenyl porphyrin is the photosensitizer；fluoropolymers have the ability to absorb oxygen and enhance the ability of type Ⅱ photodynamic pathway to produce singlet oxygen under hypoxic environment.On the other hand，the development of polymer nano-drug carriers containing type Ⅰ photosensitizers is another solution to the problem of oxygen dependence in photodynamic therapy.Similar to photothermal therapy，the effectiveness of photodynamic therapy is limited by the laser's limited penetration depth.In addition to the development of combination therapy，the development of photodynamic therapy induced by other light sources with deeper penetration is also an important research direction.These sources include X-ray，Cerenkov radiation，and etc.These new light-source-induced photodynamic therapies will provide new strategies to treat deep metastatic melanoma.(https://www.daowen.com)