Magnetoresponsive Virus‐Mimetic Nanocapsules with Dual Heat‐Triggered Sequential‐Infected Multiple Drug‐Delivery Approach for Combinatorial Tumor Therapy

Abstract

Stimuli-responsive drug-delivery systems constitute an appealing approach to direct and restrict drug release spatiotemporally at the specific site of interest. However, it is difficult for most systems to affect every cancer cell in a tumor tissue due to the presence of the natural tumor barrier, leading to potential tumor recurrence. Here, core-shell magnetoresponsive virus-mimetic nanocapsules (VNs), which can infect cancer cells sequentially and double as a magnetothermal agent fabricated through anchoring iron oxide nanoparticles in a single-component protein (lactoferrin) shell, are reported. With large payload of hydrophilic/hydrophobic anticancer cargos, doxorubicin and palictaxel, VNs can simultaneously give a rapid drug release and intense heat while applying an external high-frequency magnetic field (HFMF). Furthermore, after being liberated from dead cells by HFMF manipulation, the constructive VNs can sequentially infect neighboring cancer cells and deliver sufficient therapeutic agents to next targeted sites. With high efficiency for sequential cell infections, VNs have successfully eliminated subcutaneous tumor after a combinatorial treatment. These results demonstrate that the VNs could be used for locally targeted, on-demand, magnetoresponsive chemotherapy/hyperthermia, combined with repeated cell infections for tumor therapy and other therapeutic applications.

Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy

“…When Lf-MION suspensions (0.1 mg/mL in PBS) were treated with a high-frequency magnetic field (MF) with a frequency of 50 kHz, an obvious increase in temperature was measured ( Figure 2 j ) for various MF intensities ranging from 4 to 16 kA/m. The mechanism by which the MF induces heat from magnetic particles is through magnetic energy dissipation (Brown and Néel relaxations), which is detrimental to the crystal size and the materials 37 , 38 . The temperature increase in Lf-MIONs can be regulated by the MF strength and treatment time.…”

Novel approaches for the preparation of magnetic nanogels via covalent bonding

“…Even the size of AEMAm2 could not be exactly obtained from TEM images due to the agglomeration of the MNG particles, it seemed that AEMAm2 was larger in size than in AEMAm1. MNPs could make the water exclusion and the shrinking of MNG particles more difficult due to their rigidity, as reported by Fang et al in magneto‐responsive nanocapsules. Moreover, in the case of AEMAm1 there were no MNPs at the surface of the MNGs, while in the case of AEMAm2, MNPs were also found at the surface.…”

Enzyme-coated Janus nanoparticles that selectively bind cell receptors as a function of the concentration of glucose

“…In the context of cancer therapy, the magnetic particles proposed here could be used to kill cancer cells with magnetothermal therapy with reduced side effects. 28 Similarly bioimaging nanoprobes based on this design (e.g. MRI probes based on the proposed Janus magnetic nanoparticles) 29 could reduce background signals and improve the signal-to-noise ratio when imaging glucose-deficient tumors.…”