Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters(CTC)disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer.In this study,a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site,which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients.Targeted multiresponsive(magnetic hyperthermia and pH)nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream.A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients.The nanotheranostic system was further evaluated for the targeting property,drug release kinetics,hyperthermia and cytotoxicity against developed CTC model in vitro.In vivo model in BALB/c mice equivalent to stageⅢandⅣhuman metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system.Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Additive manufacturing of biodegradable porous orthopaedic screw

Advent of additive manufacturing in biomedical field has nurtured fabrication of complex,customizable and reproducible orthopaedic implants.Layer-by-layer deposition of biodegradable polymer employed in development of porous orthopaedic screws promises gradual dissolution and complete metabolic resorption thereby overcoming the limitations of conventional metallic screws.In the present study,screws with different pore sizes(916×918μm to 254×146μm)were 3D printed at 200μm layer height by varying printing parameters such as print speed,fill density and travel speed to augment the bone ingrowth.Micro-CT analysis and scanning electron micrographs of screws with 45%fill density confirmed porous interconnections(40.1%)and optimal pore size(259×207×200μm)without compromising the mechanical strength(24.58±1.36 MPa).Due to the open pore structure,the 3D printed screws showed increased weight gain due to the deposition of calcium when incubated in simulated body fluid.Osteoblast-like cells attached on screw and infiltrated into the pores over 14 days of in vitro culture.Further,the screws also supported greater human mesenchymal stem cell adhesion,proliferation and mineralized matrix synthesis over a period of 21 days in vitro culture as compared to non-porous screws.These porous screws showed significantly increased vascularization in a rat subcutaneous implantation as compared to control screws.Porous screws produced by additive manufacturing may promote better osteointegration due to enhanced mineralization and vascularization.