The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers

Abstract

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposomes.

A nanoparticle formulation that selectively transfects metastatic tumors in mice

“…Given that the shell dose mediates both toxicity and transfection efficiency, we wondered whether replacing the LPEI88 in the shell with a less-toxic LPEI might reduce toxicity but preserve in vivo transfectability. Composite nanoparticles containing two types of cationic polymers described in the literature (37,38), along with the data presented in Tables S1 and S2, inspired us to synthesize composite LPEI-based nanoparticles that take advantage of both the high transfectability of LPEI88 and the low toxicity of LPEI2.5. Thus, a nanoparticle core was formed by incubating DNA with LPEI88, and a shell around this core was formed by incubating this core with excess LPEI2.5.…”

Phospholipid Encapsulated AuNR@Ag/Au Nanosphere SERS Tags with Environmental Stimulus Responsive Signal Property

“…Finally, they were trapped in the endosome and then transported to lysosome encountering an acidic environment with pH about 5. 46,47 In our case, the location of lipid-coated tags was verified by fluorescence colocalization using green fluorescence of LysoTracker DND-26 that could specifically stain the lysosome and the red fluorescence of Cy7 or DiD dye in the tags. As shown in Figure S8, images in columns a−d were bright-field images, tag fluorescence images, LysoTracker Green DND-26 fluorescence images, and the merged images, respectively.…”

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

“…Afterwards, these nanoparticles induce the endosomal escape by disruption of the endosome membrane and upon degradation release the siRNA directly in the cytosol (Figure 13) [134]. Other types of nanoparticles capable to encapsulate siRNA are mesoporous silica nanoparticles with large pores [31,135,136] embedding the siRNA inside them under strong dehydrating conditions [63,137]. Carrying the siRNA encapsulated shows some advantages over ionic adsorption [65], including avoiding the use of large amounts of positively charged substances that can increase toxicity 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 30 and the fact that more groups are available on the surface for the effective attachment of targeting molecules, thus improving the system's specificity.…”