<p>^99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

Abstract

Background: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)loaded nanoparticle of 99m Tc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics. Materials and Methods: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice. Results: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/ mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99m Tc. The SPECT images showed that 99m Tc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs. Conclusion: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99m Tc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy

“…The pH-responsive drug release could be attributed to the presence of CHEMS in the hybrid-liposome, which would be protonated and change the structure in an acidic environment [ 65 ]. This would result the prepared NPs unstable at acidic environments, accelerating the release of FTY720.…”

In Vivo Efficacy and Toxicity of Curcumin Nanoparticles in Breast Cancer Treatment: A Systematic Review

“…In addition, no biochemical modifications or structural damage were observed in the liver and kidneys ( 40 ). Huang and co-workers ( 48 ) encapsulated curcumin in pH-sensitive polymeric NPs and showed a significant reduction in tumor volume followed by increased survival time ( Table 1 ) ( 48 ). Internalization of NPs can be mediated or not by active targeting ligands (depending on the mechanism triggered), and it occurs mainly through endocytosis pathways where the main mechanisms comprise a) clathrin-mediated endocytosis; b) caveolae-mediated endocytosis, for NPs up to 200 nm; c) macropinocytosis; and d) other clathrin and caveola-independent endocytosis for NPs with sizes between 250 nm and 3 µm ( 70 , 71 ).…”

“…Cell cycle arrest by free curcumin has also been described and is potentially associated with its antiproliferative effects ( 74 ). Regarding the antitumor mechanisms reported in the included studies, Cur-NPs were shown to induce at least tumor apoptosis, necrosis, and/or cell proliferation blockage in in vivo breast cancer models ( 26 , 28 , 30 , 34 , 36 , 37 , 40 , 41 , 45 , 48 ).…”

“…This process led to exclusion of 50 articles according to exclusion criteria (Table S2). In the end, 26 articles were maintained and included in this systematic review (Table 1) (25)(26)(27)(28)(29)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). A flowchart detailing this process is shown in Figure 3.…”

Prospects of Curcumin Nanoformulations in Cancer Management

“…Huang and colleagues [154] used membrane dialysis to fabricate self-assembled 99mTcradiolabeled CUR-NPs with HA-cholesteryl hemisuccinate conjugates and D-a-TPGS. The NPs (144 nm, −21.25 ± 1.66 mV, 84.0 ± 5.0% EE) inhibited 4T1 cell growth by twofold compared CUR (IC 50 values: 38 µg/mL vs. 77 µg/mL).…”