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Manganese-based nanomaterials are an emerging new class of magnetic resonance imaging (MRI) contrast agents (CAs) that provide impressive contrast abilities. MRI CAs that can respond to pathophysiological parameters such as pH or redox potential are also highly in demand for MRI-guided tumor diagnosis. Until now, synthesizing nanomaterials with good biocompatibility, physiochemical stability, and good contrast effects remains a challenge. This study investigated two new systems of calcium/manganese cations complexed with either alginate−polydopamine or alginate−dopamine nanogels [AlgPDA(Ca/Mn) NG or AlgDA(Ca/Mn) NG]. Under such systems, Ca cations form ionic interactions via carboxylic acids of the Alg backbone to enhance the stability of the synthetic nanogels (NGs). Likewise, complexation of Mn cations also increased the colloidal stability of the synthetic NGs. The magnetic property of the prepared CAs was confirmed with superconducting quantum interference device measurements, proving the potential paramagnetic property. Hence, the T 1 relaxivity measurement showed that PDA-complexed synthetic NGs reveal a strong positive contrast enhancement with r 1 = 12.54 mM −1 •s −1 in 7.0 T MRI images, whereas DA-complexed synthetic NGs showed a relatively lower T 1 relaxivity effect with r 1 = 10.13 mM −1 •s −1 . In addition, both the synthetic NGs exhibit negligible cytotoxicity with >92% cell viability up to 0.25 mM concentration, when incubated with the mouse macrophage (RAW 264.7) and HeLa cells, and high biocompatibility under in vivo analysis. The in vivo MRI test indicates that the synthetic NG exhibits a high signal-to-noise ratio for longer hours, which provides a longer image acquisition time for tumor and anatomical imaging. Furthermore, T 1 -weighted MRI results revealed that PEGylated AlgPDA(Ca/Mn) NGs significantly enhanced the signals from liver and tumor tissues. Therefore, owing to the enhanced permeability and retention effect, significantly enhanced in vitro and in vivo imagings, low cost, and one-pot synthesis method, the Mn-based biomimetic approach used in this study provides a promising and competitive alternative for noninvasive tumor detection and comprehensive anatomical diagnosis.

Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV–Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

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Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.