Thermally responsive nanoparticle-encapsulated curcumin and its combination with mild hyperthermia for enhanced cancer cell destruction

Abstract

In this study, thermally responsive polymeric nanoparticle-encapsulated curcumin (nCCM) was prepared and characterized. The nCCM is ~22 and 300 nm in diameter at 37 and 22 °C, respectively. The smaller size of the nCCM at 37 °C was found to significantly facilitate its uptake in vitro by human prostate adenocarcinoma PC-3 cancer cells. However, the intracellular nCCM decreases rapidly (rather than plateaus) after reaching its peak at ~1.5 h during a 3-day incubation of the PC-3 cells with nCCM. Moreover, a mild hyperthermia (with negligible cytotoxicity alone) at 43 °C applied between 1 and 1.5 h during the 3-day incubation not only increases the peak uptake but also alters intracellular distribution of nCCM (facilitating its delivery into cell nuclei), which helps to retain a significantly much higher level of intracellular curcumin. These effects of mild hyperthermia could be due in part to the thermal responsiveness of the nCCM: they are more positively charged at 43 °C and can be more easily attracted to the negatively charged nuclear membrane to enter nuclei as a result of electrostatic interaction. Ultimately, a combination of the thermally responsive nCCM and mild hyperthermia significantly enhances the anticancer capability of nCCM, resulting in a more than 7-fold decrease in its inhibitory concentration to reduce cell viability to 50% (IC50). Further mechanistic studies suggest injury pathways associated with heat shock proteins 27 and 70 should contribute to the enhanced cancer cell destruction by inducing cell apoptosis and necrosis. Overall, this study demonstrates the potential of combining mild hyperthermia and thermally responsive nanodrugs such as nCCM for augmented cancer therapy.

Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy

“…3b). According to the relevant literature, mild hyperthermia (38e42 C) has no cytotoxic effect on cells [35]. These experimental results show that the Lipos-HMs prepared herein could convert magnetic energy into local heat in an external magnetic field, increasing the local temperature, including the Lipos that were adsorbed on HMs and their PLGA shell matrices.…”

Microwave Cavity with Controllable Temperature for In Vitro Hyperthermia Investigations

“…A key challenge prior to employing hyperthermia is to carry out in vitro assessment of the procedure's efficacy [4][5][6][7]. For our case, the goal is to assess fullerene agents to reduce heating time and improve hyperthermia efficacy.…”

Supercritical carbon dioxide-developed silk fibroin nanoplatform for smart colon cancer therapy

“…The chemical structure of CM-SF NPs was confirmed by FTIR results; it is believed that the incorporated CM most likely interacted with the hydrophobic residues in the silk nanoplatforms. 22,26 Moreover, the 3,495 cm -1 (O-H) peak in CM shifted to 3,290 cm -1 , suggesting that CM linked to the SF nanoplatforms, maybe via hydrogen bonds. 19 Importantly, the solubility of CM-SF NPs was greatly improved, which was mainly due to size reduction, supersaturation of CM, water solubility of the SF nanoplatform, better dispersibility and wettability of CM, and hydrogen bonds between CM and the SF nanoplatform.…”

“…27,28 The intracellular uptake result of CM-SF NPs is in agreement with previous studies. 26,29 In those studies, the introduction of SF improved the retention of loaded drugs in cancer cells, thus leading to a higher anticancer efficacy. In our opinion, there are two reasons for the better cellular uptake Figure 5 anticancer mechanism of cM-sF NPs against colon cancer cells.…”