Natural
killer (NK) cell-based immunotherapy has been considered
a promising cell-based cancer treatment strategy with low side effects
for early tumors and metastasis. However, the therapeutic efficacy
is generally low in established solid tumors. Ex vivo activation of NK cells with exogenous cytokines is often essential
but ineffective to generate high doses of functional NK cells for
cancer treatment. Image-guided local delivery of NK cells is also
suggested for the therapy. However, there is a lack of noninvasive
tools for monitoring NK cells. Herein, magnetic nanocomplexes are
fabricated with clinically available materials (hyaluronic acid, protamine,
and ferumoxytol; HAPF) for labeling NK cells. The prepared HAPF–nanocomplexes
effectively attach to the NK cells (HAPF-NK). An exogenous magnetic
field application effectively achieves magneto-activation of NK cells,
promoting the generation and secretion of lytic granules of NK cells.
The magneto-activated HAPF-NK cells also allow an MR image-guided
NK cell therapy to treat hepatocellular carcinoma (HCC) solid tumors
via transcatheter intra-arterial infusion. Suppressed tumor growth
after the treatment of IA infused magneto-activated NK cells demonstrated
a potential enhanced therapeutic efficacy of image guided local delivery
of magneto-activated HAPF-NK cells. Given the potential challenges
of NK cell cancer immunotherapy against established solid tumors,
the effective NK cell labeling with HAPF, magneto-activation, and
MRI contrast effect of NK cells will be beneficial to enhance the
NK cell-therapeutic efficacy in various cancers.
A polyelectrolyte block copolymer, poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) (P(Aspg-Im)-PEG), with several advantages such as an easy synthesis, having a high molecular weight and the buffer capacity of a zwitterionic polymer backbone compared to poly(histidine) backbones, was presently investigated to evaluate its feasibility as a pH sensitive anticancer nanomedicine. Doxorubicin (DOX) loaded P(Asp-g-Im)-PEG micelles (DPHAIM) were prepared by the bottom flask and diafiltration methods, forming stable pH sensitive nano-systems. DPHAIM with a 28% loading capacity displayed a pH dependent behavior with respect to drug release and cytotoxicity. At pH values below 7.0, the cumulative DOX release and cell cytotoxicity were increased compared to those at physiological pH.Animal imaging after intravenous administration of the micelles revealed their accumulation by passive targeting to tumor tissue compared to other normal tissues. This pH sensitive nanovehicle based on P(Asp-g-Im)-PEG is implicated as a promising anticancer nanomedicine with less toxicity on normal tissues for effective tumor treatment.
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