Mutifunctional Nano-bioconjugates For Cancer Cell Imaging, Controlled Drug Release And Therapy

Malignant tumor (cancer) is one of the principal diseases which threat the humanhealth. In recent years, with the deterioration of human living environment, there was agrowth trend in the morbidity of cancer. Although the clinical arsenal in treating cancerhas been greatly extended in recent years with the discovery of new drugs and theimprove of therapeutic modalities, the three main approaches, surgicalnresection,radiation and chemotherapy, still occupy a leading position. Most research focus on howto improve the efficacy of chemotherapy which is widely considered the most promisingapproach in cancer therapy. But serious side effects are unavoidable in traditionalchemotherapy treating. Because nanocarriers have a lot of advantages such as goodstability, biocompatibility and easy functionalization, combining nanocarriers withtherapeutic agents for targeted delivery and controlled release attracts much attention.Over the past decade, the use of delivery platforms has attracted attention as researchersshift their focus to new ways to deliver therapeutic and/or diagnostic agents and awayfrom the development of new drug candidates. Therefore, there is great significance todevelop steady, biocompatible and release controlled nanocarrier and now this is theresearch hotspot.The gold nanorods (AuNRs) have strong absorption in the NIR region and themaximum absorption peak can be adjusted, so AuNRs can be employed as the local heatsources when irradiated with an NIR laser through the photothermal effect. Meanwhile,the near-infrared light have advantage of deep-tissue penetration and avoids thecytotoxic effects. Mesoporous silica nanoparticles (MSNs) are considered to be idealcandidates for drug delivery because of their high surface area, large pore volume, notpharmacological activity, good biocompatibility and easy functionalization. DNAmolecular, as the biomolecules, provides many advantages, such as good biocompatibility and better cellular uptake, so it is chosen as the bio-valve.In this study, the recent research progress and development tendency of theapplication of nanocarriers in biotechnology are reviewed. Based on the above, by usingbiocompatible mesoporous silica accompany with gold nanorods and DNA molecular,we developed a series of nanocarriers for cancer imaging and treating, and carried outthe following work:1.A near-infrared (NIR) light-triggered nanocarrier was developed for intracellularcontrolled release with good stability, high nuclease resistance, and goodbiocompatibility. The nanocarrier consists of a gold nanorod core and mes-oporoussilica shell, capped with reversible single-stranded DNA valves, which are manipulatedby switching between the laser on/off states. Single-stranded DNA moleculars arelinked to the amino modified MSNs as the valves. The gold nanorods (AuNRs) havestrong absorption in the NIR region and can generate heat through the photothermaleffect. Upon laser irradiation, the valves of the nanocarrier open and the cargomolecules can be released from the mesopores. When the NIR laser is turned off, thevalves close and the nanocarrier stops releasing the cargo molecules. The releaseamount of the cargo molecules can be controlled precisely by adjusting the irradiationtime and the laser on-off cycles. Confocal fluores-cence imaging shows that thenanocarrier can be triggered by the laser irradi-ation and the controlled release can beaccomplished in living cells. Moreover, the therapeutic effect toward cancer cells canalso be regulated when the chemotherapeutic drug doxorubicin is loaded into thenanocarrier.2. We developed a novel smart nanocarrier which can control drug releaseautonomously depend on the body temperature. We chose mesoporous silica as theplatform for drug loading and single-stranded DNA moleculars are linked to the aminomodified MSNs as the valves.. DNA moleculars can absorbe on the surface of theMSNs through the electrostatic interaction which act as the valves. In this research, wefound that the critical temperature at which DNA the electrostatic interaction was destroyed and one end of DNA moleculars separated from the MSNs surface changedwith the length of the DNA molecular. We studied the DNA molecular which had10,15,20,30,40bases, respectively. And we drew the conclusion that the critical temperatureincreased with the number of bases of DNA molecular being more. Then we chose theDNA molecular which had15bases and whose critical temperature was39oC as the bestpoint to do the further researches. When human bodies suffer from inflammation and thebody temperature rises above39oC, the DNA valves open autonomously resulting in thedrug release.Then, when the inflammation is cured, and the body temperature goesdown, the DNA valves return to the original state(off), the drug release stops. Thus, thenanocrriers can control the drug release completely autonomously depending on thephysical condition regardless of any other extrinsic factors, and avoiding the side effectproduced by extrinsic stimulant.