New folate-functionalized biocompatible block copolymer micelles as potential anti-cancer drug delivery systems

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

“…More recently, pH-sensitive polymeric carriers have been used in targeted antitumor drug delivery [14][15][16][17][18][19][20][21][22][23][24][25], based on intrinsic differences between various solid tumors and the surrounding normal tissues in terms of their relative acidity [26]. The extracellular pH (pH e ) in most tumors is more acidic (pH 6.5-7.2) than in normal tissues [27][28][29].…”

“…Hydrazone and acetal bonds between the drug and the micelles can be cleaved by acidic pH [14][15][16], however these bonds are more labile at endo/lysosomal pH (pH 5.0-5.5) than at tumor pH e to accelerate drug release from the micelles [14][15][16]. On the other hand, smart micelles showing a pH-induced interior structural change [17][18] or physical destabilization [19][20][21][22][23][24][25] have recently been investigated and showed a high sensitivity to tumor pH e . The physical change in the drugcarrier [17][18][19][20][21][22][23][24][25] seems more tunable to recognize small differences in pH like tumor pH e , compared to the systems that rely on chemical bonds [14][15][16].…”

“…On the other hand, smart micelles showing a pH-induced interior structural change [17][18] or physical destabilization [19][20][21][22][23][24][25] have recently been investigated and showed a high sensitivity to tumor pH e . The physical change in the drugcarrier [17][18][19][20][21][22][23][24][25] seems more tunable to recognize small differences in pH like tumor pH e , compared to the systems that rely on chemical bonds [14][15][16]. Furthermore, translating the non-specific nature of cationic HIV Tat peptide to acidic solid tumor-specific by pH-dependent electrostatic shielding/deshielding with polymeric micelles is an attractive concept [31].…”

Poly(benzyl-L-histidine)-b-Poly(ethylene glycol) Micelle Engineered for Tumor Acidic pH-Targeting, in vitro Evaluation

“…Recently, a pH-sensitive polymeric micelle system has been potentially used for targeted antitumor drug delivery, 5,6,[22][23][24][25][26][27][28][29][30][31] based on the observation that one of the consistent differences between various solid tumors and the surrounding normal tissue is the acidity of the surrounding tissue. 32 The extracellular pH (pH e ) in most tumors is more acidic (pH, 6.5-7.2) than in normal tissues.…”

“…The benzyl (Bz) group (used as a protecting group for polyHis synthesis) 5,6,29 remaining in polyHis, as shown in Figure 1, may be useful in tuning drug release behaviors of the polymer micelle with pH. 5,6,[22][23][24][25][26][27][28][29][30][31] For proof of this concept, we examined the pH-sensitive properties of the polyBz-His-b-PEG micelles and monitored pHdependent cell cytotoxicity against human breast carcinoma cells (MCF-7).…”