Phototherapy and Chemotherapy Combined Nano-platforms for Disease Treatment

Author:Sun Pan Pan

Supervisor:ren jin song


Degree Year:2019





Nowadays,bacterial infections and tumors have become the two most serious threats to human health.Antibiotics and small molecule anticancer drugs are commonly used in the treatment of bacterial infections and tumors.However,most of the antibiotics and anticancer drugs are hydrophobic and without specificity.The rapid immunological clearance in circulation,and unsatisfied disease targeting property of drugs severely limited their further application.Considering the EPR effect of nanomaterials,nanocarrier can be employed to construct novel drug delivery systems to improve the targeting ability of drugs to bacterial infected sites or tumor tissues and enhance their therapeutic effect.However,due to the drug-resistance of bacteria and cancer cells,it often requires larger drug doses for chemotherapy to realize effective therapy.As an emerging strategy,phototherapy can cause the generation of reactive oxygen species or hyperthermia by using specific laser,exhibiting excellent photodynamic or photothermal effect.Due the non-invasive and spatiotemporal controllable ability of phototherapy,it has attracted more and more attentions.Combining chemotherapy with phototherapy in one system can exert their advantages simultaneously,eradicate bacterial infections and tumor with high efficacy in a lower drug doses.What’s more,it’s also necessary to explore effective strategies for enhancing the penetration of nanomedicines in tumors.Herein,we developed a series of novel strategies with synergetic photo-chemotherapy for effectively treatment of bacterial infections and tumor:1.For the first time,a novel "on-demand" phytochemical delivery nanoplatform was constructed to treat the MDR bacterial infection.As a green antibacterial agent,plant essential oils(PEO)are harmless to environment and animals and have broad-spectrum antibacterial effect via various mechanism,which is not easy to cause bacterial resistance.This nanoplatform(CA@AuMN-HA)would greatly enhance the bioavailability and selectivity of the encapsulated PEO and significantly improve their bactericidal effect after combination with photothermal ability of the nanocarrier.Meanwhile,the synergistic system could effectively eliminate the drug-resistant bacteria with negligible biotoxicity.Given the increasing risk of antibiotic resistance,we believe this phytochemical encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.2.For the first time,we develop a near-infrared(NIR)light mediated self-destructive MDS for enhanced tumor-tropic synergistic therapy.This system possesses large drug loading capacity and prevents drug leakage to maintain the function and activity of carrier cells during circulation.After arriving to the tumor site,it exhibits multiple enzyme activities to generate oxygen,alleviating the hypoxia of the tumor.Under near-infrared light irradiation,the carrier cells were destructed to sufficiently release the drug-loaded nanocarriers.Then the nanocarriers respond to the low pH and excessive H2O2 in the tumor cells to release drugs and produce Mn2+.Mn2+ catalyzes the Fenton-like reaction to produce ROS,further enhanced the therapy efficacy.In addition,the photothermal and photodynamic effects of nanocarriers under near-infrared light can be used in coordination with chemotherapy for enhanced synergistic therapy.It is worth nothing that the NIR light-mediated self-destruction of the carrier cells prevents the tumor-promoting transformation of the carrier macrophages.In this system,the cell viability and tumor-tropic migration ability of macrophages were not significantly affected after endocytosis of drug-loaded nanosystem.Due to the above advantages,the macrophage-based drug delivery system can significantly inhibit the growth of 4T1 cell-induced breast tumors in mice,or even completely eliminate them.3.We have constructed a non-enzymatic target recycling amplification approach for label-free and high-sensitive detection of telomerase activities based on the DNA-fueled molecular machine.The TRP,acting as a catalyst,triggers the operation of the molecular machine and results in the hybridizations between H1 and H2,leading to the reuse of TRP and the generation of massive G-quadruplex structures.Our system achieves significant signal amplification for telomerase detection even down to a single cell.In addition,the method offers a credible system for selectively distinguishing different telomerase levels in various cell lines and screening the telomerase inhibitors.Furthermore,the introduction of the DNA-fueled molecular machine into the sensing system could realize the recycling process and significant fluorescence signal amplification without the involvement of any enzymes.Also,this approach doesn’t require any modification and takes less than 2 h to perform.