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Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30-45 nm) comprising doxorubicin-superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM s) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αβ integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T contrast.

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Fabricating nanofibrous scaffolds with robust blood compatibility remains an unmet challenge for cardiovascular applications since anti-thrombogenic surface coatings did not withstand physiological shear force. Hence, the present study envisages the influence of smooth and porous topographies of poly(lactic acid) (PLA) nanofibers on hemocompatibility as it could offer time-independent blood compatibility. Further, recent studies have evolved to integrate various contrasting agents for augmenting the prognostic properties of tissue engineered scaffolds; an attempt was also made to synthesize Curcumin-superparamagnetic iron oxide nanoparticle complex (Cur-SPION) as a contrasting agent and impregnated into PLA nanofibers for evaluating the blood compatibility. Herein, electrospun nanofibers of PLA with different topographies (smooth and porous) were fabricated and characterized for surface morphology, zeta potential, fluorescence, and crystallinity. The scaffolds with smooth, porous and rough surface topographies were thoroughly investigated for its hemocompatibility by evaluating hemolysis percentage, platelet adhesion, in vitro kinetic clotting time, serum protein adsorption, plasma recalcification time (PRT), capture and release of erythrocytes. Although the nanofibers of all three groups showed acceptable hemolytic percentage (HP < 5%), the adhered RBCs on Cur-SPION based fibers undergo morphological transformation from biconcave discocytes to echinocytes with cube-like protrusions. On the contrary, no morphological changes were observed in RBCs cultured on smooth and porous nanofibers. Porous fibers exhibited excellent anti-thrombogenic property and adhered lesser platelets and maintained the discoidal morphology of native platelets. Cur-SPION integrated PLA nanofibers showed inactivated platelets with anti-thrombogenic activity compared to smooth nanofibers. In conclusion, PLA nanofibers porous topography did not affect the RBC membrane integrity and maintained discoidal morphology of platelets with superior anti-thrombogenic activity. However, smooth and Cur-SPION integrated PLA nanofibers were found to activate the platelets and deform the RBC membrane integrity, respectively. Hence, the nanofibers with porous structures provide an ideal topography for time-independent hemocompatibility.