Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier.

The blood-brain barrier (BBB) and blood-tumor barrier (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities to overcome these barriers and enhance drug penetration into the brain parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic field, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery involves using engineered cells as carriers for nanoparticles, taking advantage of their intrinsic migratory and homing capabilities to facilitate the transport of therapeutic payloads across BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, coupled with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery exploits magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive avenue to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM.

Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process is demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nanostar loaded with triamcinolone is conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nanostar significantly elevates the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, is downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell is inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nanostar (Edu-MSCs-AuS-TA) promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain, improve general locomotor activity, and more importantly, induce cartilage regeneration even for severe stages of arthritis model.