LRP1-upregulated nanoparticles for efficiently conquering the blood-brain barrier and targetedly suppressing multifocal and infiltrative brain metastases

Overcoming Mfsd2a‐Mediated Low Transcytosis to Boost Nanoparticle Delivery to Brain for Chemotherapy of Brain Metastases

“…Both free DOX and DOX@NPs revealed negligible drug accumulation in all lesions. DOX@HA accumulated in some lesions but with low efficiency, which was consistent with previous report, [ 15b ] and can be explained by the relatively intact BBB in early brain metastases and the poor enhanced‐permeation and retention effect. TM@TTP and DOX@TTP, capable of efficiently crossing the intact BBB, showed unbiased accumulation in both normal brain and metastatic foci.…”

“…Poly(lactic‐ co ‐glycolic acid)–poly( ε ‐carbobenzoxy‐ l ‐lysine) (PLGA–PLL) was synthesized as starting material of nanocarrier via coupling PLGA with PLL using DCC and DMAP. [ 15 ] Drug‐loaded NPs were prepared using ultrasonic emulsion solvent evaporation method. The hydrophilic PLL was exposed at the surface of NPs for conjugation with a‐malemidyl‐u‐ N ‐hydroxysuccinimidyl polyethyleneglycol, MW5000 (NHS‐PEG‐MAL) to display PEG.…”

“…In our previous work, “minoxidil‐boosted” HA‐mediated active tumor targeting acted on large metastasis with the damaged BBB and showed limited effect on micrometastases with the intact BBB. [ 15b ] The therapeutic improvement can be ascribed to the efficient drug delivery based on the synergistic effect between efficient BBB passing and HA‐mediated active tumor targeting. For in vivo systemic toxicity, no significant loss of body weight was observed during the treatment period and before the worsening of brain metastases (Figure 6B).…”

Nanomedicine Revisited: Next Generation Therapies for Brain Cancer

“…reported the design and use of polymeric nanoparticles that are functionalized with angiopep‐2, a ligand known to increase transcytosis and BBB penetration ( Figure A). [ 284 ] Next, the nanoparticles were loaded with simvastatin to upregulate the expression of LRP‐1, a receptor of angiopep‐2 on brain microvascular endothelial cells and metastatic cancer cells to enhance BBB and tumor penetration (Figure 11A). [ 284 ] Finally, the nanoparticles were loaded with doxorubicin and the systemic administration of these nanoparticles prolonged survival of metastatic brain cancer‐bearing mice (Figure 11B).…”

“…[ 284 ] Finally, the nanoparticles were loaded with doxorubicin and the systemic administration of these nanoparticles prolonged survival of metastatic brain cancer‐bearing mice (Figure 11B). [ 284 ] Wu et al. achieved similar efficacy and decreased tumor burden with doxorubicin‐loaded nanoparticles; however, this group employed ultrasound‐mediated hyperthermia after nanoparticle injection to improve penetration and tumor killing rather than functionalization of the nanoparticles themselves.…”