Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy.In this study,a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy(SERS).The Fe3O4@Au@Ag nanoparticles(NPs)deposited graphene oxide(GO)nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid(4-MPBA)to form SERS probes(GO-Fe3O4@Au@Ag-MPBA).Furthermore,doxorubicin(DOX)is attached to SERS probes through a pH-responsive linker boronic ester(GO-Fe3O4@Au@Ag-MPBA-DOX),accompanying the 4-MPBA signal change in SERS.After the entry into tumor,the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal.Thus,the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra.Additionally,the strong T2 magnetic resonance(MR)signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy(PTT).Altogether,this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting,pH-sensitive drug release,SERS-traceable detection and MR imaging,endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Polymeric prodrug for bio-controllable gene and drug co-delivery

A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.