Multifunctional SPIO Nanocarrier Dual-Mode Imaging-Guided Chemo-Photothermal Therapy On Transdermal Treatment Of Superficial Tumors

Malignant tumors continue to be a leading threat to human health.Nanomedicine is a current research hotspot in cancer treatment due to its advantages such as targeted drug delivery,controlled drug release and improved bioavailability.Although various multifunctional nanoparticles have been developed,the controversy of the efficient delivery of nanomaterials through intravenous injection is still ongoing.Transdermal delivery is an attractive approach for the superficial tumors,which can directly deliver external therapeutic drugs to the tumor site with high drug bioavailability and minimized systemic toxicity.Super-paramagnetic iron oxide nanoparticles(SPIO)are a novel imaging and drug delivery system with intense magnetic responsiveness,strong drug-loading capacity and good biocompatibility.Although SPIO has the potential as a transdermal drug delivery vector,there is limited in the transdermal treatment of tumors due to the barrier function of skin.Transdermal peptide TD can enhance the transdermal efficiency of nanomedicine,and TD-modified SPIO nanocarriers have the potential to overcome the skin barrier to SPIO.In addition,nanoparticle-based multimodal combination therapy is an emerging way to treat cancer,and imaging technology is essential for tracking the distribution of nanomodules in vivo.Therefore,it is of great significance to develop TD-modified nanomedicines based on SPIO nanoparticles to achieve imaging-guided multimodal transdermal treatment of superficial tumors.We successfully prepared(+)T-SiDs nanoparticles by modifying SPIO with cationic phospholipids and transdermal enhanced peptide TD through an optimized solvent replacement method,and simultaneously loading near-infrared probes and chemotherapeutic drug doxorubicin.The TD-modified(+)T-SiDs with a positive surface charge can achieve high-efficiency nanoparticle permeation through high-efficiency transdermal efficiency,and realize dual-modal MR/NIR imaging-guided synergistic chemo-photothermal therapy of superficial tumors.The main contents are as follows:Firstly,the performance of(+)T-SiDs nanoparticles was prepared and characterized in vitro:according to TEM,SEM and DLS experiments,(+)T-SiDs are uniform in size.The hydrated particle size is about 50 nm,and the particle surface is positively charged,and it can be stored stably for more than one month at low temperatures.Further evaluations showed that(+)T-SiDs have in vitro experimental evaluations of their drug encapsulation rate,drug loading rate,drug release,cell uptake,photothermal performance and near-infrared imaging.The experimental results show that(+)T-SiDs nanoparticles have a uniform,small size,can maintain stability for a long time,good photothermal performance and photothermal stability,excellent tumor cell targeting ability,and can be controlled drug release ability and efficient skin penetration ability;in addition,its encapsulation rate is up to 90%.Next,the in vitro and in vivo MR/NIR dual-mode imaging effects were explored:The relaxivity coefficient(r2 value)was calculated to be 185.18 mM-1 s-1,which was approximately 1.3-fold of the commercial MR contrast agents of Resovist(143 mM-1 s-1).The in vivo MR imaging capability of the(+)T-SiDs nanoparticles showed great potential for guiding chemo-photothermal therapy in the treatment of tumors.The results of near-infrared fluorescence imaging also confirmed that it was a potential near-infrared fluorescence imaging probe.Finally,based on a mouse breast cancer model,it was evaluated that the therapeutic effect of synergistic chemo-photothermal therapy treatment for superficial tumor in vivo:(+)T-SiDs were daubed on mouse breast cancer models by transdermal delivery for combined chemo-photothermal therapy to verify the efficacy of tumor treatment with(+)T-SiDs.The results show that(+)T-SiDs nanoparticles can efficiently penetrate the skin to achieve accumulation at the tumor site;under the synergistic effect of photothermal and chemotherapy,they can significantly inhibit or even eradicate tumors,and will not cause obvious damage to major organs(heart,liver,spleen,lungs and kidneys).In this paper,the(+)T-SiDs nanoparticles exhibited excellent transdermal effect,dual-modal NIR/MR imaging capacity and prominent chemo-photothermal theray synergism,which significantly inhibited the tumors of the mice.