Tumor targeting and microenvironment-responsive multifunctional fusion protein for pro-apoptotic peptide delivery

Phenylboronic Acid Modification Augments the Lysosome Escape and Antitumor Efficacy of a Cylindrical Polymer Brush-Based Prodrug

“…As well-documented, after intravenous injection, the positively charged materials are prone to opsonization and hence have short blood circulation and little opportunity to reach tumors. 4,6,30 The strategy of charge reversal can keep the materials neutral or anionic in blood circulation and trigger cationization at disease sites; however, sophisticated design and preparation are needed and the efficient charge reversal at the target sites is still a huge challenge. 31 For the case of fusogenic peptides, their ability to escape from lysosomes would be diminished after conjugation to nanomaterials, and their high cost and quite complicated preparation may also limit greatly their applications.…”

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

“…Unsatisfactory in vivo efficacy limits the clinical transformation of widely used gene carriers such as lipoplex and polyplex. Against this disadvantage, nanotechnology has been skillfully used to construct various therapeutic gene delivery systems, typically such as PEG shielded MMP sensitive CPPs 101 , envelope-type non-viral nanodevice for liver-targeting siRNA delivery 102 , polyethylenimine (PEI)-based chlorotoxin-targeted melittin gene delivery to MMP-2 positive prostate cancer cells 103 , MMP-2-cleavable PEG- β -cyclodextrin-PEI nanoconjugates for tumor suppressor microRNA miR-34a-induced breast cancer treatment 104 , MMP-2-cleavable motif-included short amphiphilic peptide hydrogels for cell-demanded remedial peptide release into cervical cancer cells 105 , MMP-2-sensitive cytotoxic peptide‒dendrimer conjugates for enhanced intracellular enrichment, deep tumor penetration, promoted cell apoptosis and anti-glioblastoma (GBM) performance 106 , multifunctional fusion proteins for targeting the release of interferon gamma 107 , pro-apoptotic peptide 108 , or cytotoxic enediyne 109 into MMP-2-dysregulated tumor tissues. Moreover, some promising nanocomplexes were also developed for the co-delivery of heat shock protein 70-specific siRNA (siHSP70) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) 110 , sequentially responsive dual-targeted peptide presentation 111 , MMP-2/glutathione (GSH) dual-stimulated DOX/miRNA-34a co-delivery to tumor mass 112 , and MMP-2-triggered on-demand submission of neurotrophic growth factors (NTFs) to induce neural differentiation 113 .…”

“…DOX-encapsulated gold nanoclusters were presented for computed tomography (CT) imaging-visualized cancer chemotherapy 123 . The above MMP-2-encouraged representative achievements in cancer theranostics are summarized in Table 2 23 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ...…”

Phenylboronic acid modification augments the lysosome escape and antitumor efficacy of a cylindrical polymer brush-based prodrug

“…Although the approaches mentioned above can achieve lysosome escape, they have respective noticeable drawbacks. As well documented, after intravenous injection, the positively charged materials are prone to opsonization and hence have short blood circulation and little opportunity to reach tumors 4,6,30 . The strategy of charge reversal can keep the materials neutral or anionic in blood circulation and trigger cationization at disease sites, however, sophisticated design and preparation are needed and the efficient charge reversal at the target sites is still a huge challenge 31 .…”