Recent progress in tumor pH targeting nanotechnology

Abstract

pH-sensitive polymeric micelles and nanogels have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms by endosomal or lysosomal acidity plus endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. This review highlights recent progress of the pH-sensitive nanotechnology developed in Bae research group.

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

“…This implies that negligible amounts of Gefi tinib were retained in the dialysis bags; after 24 h. However at pH 7.5, a small population positive for fl uorescence was observed; indicating that some drug molecules remained encapsulated, confi rming sustained release of Gefi tinib from H-AFt at physiological pH levels. [ 36 ] The in vitro results indicate that encapsulation of Gefi tinib within an H-AFt cage could provide a facile route to targeted drug delivery and release in vivo. Recognition of H-AFt by TfR1 of cancer cells allows encapsulated cargo to be selectively internalized into cancer cells via TfR1 mediated endocytosis [ 3,4 ] and has successfully been utilized for targeted delivery of, e.g., MRI imaging agents.…”

“…[ 5 ] The overall pH range within a tumor environment is 6.5-7.2 where as normal cells possess a pH range of 7.2-7.4, allowing pH controlled release. [ 36 ] Further, the pH-dependent release of cargo could offer additional advantage for applications in stomach cancers, where an acidic environment would enhance drug release from the AFt cavity. Hence, it was examined whether a more acidic in vitro environment would promote effective release of Gefi tinib from its H-AFt cage.…”

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

“…This compound was added as a modifier into the formulation in order to achieve a greater antitumor activity of the encapsulated drug. The anionic amphiphile derived from N α ,N ε -dioctanoyl lysine with a sodium counterion (77KS) have pH-sensitive membrane-lytic behavior and low cytotoxicity (Nogueira et al 2011a), suggesting that it may be a specific adjuvant with ability to destabilize the endosomal membrane in the mildly acidic environment and, thus, release more specifically and efficiently the drug inside the malignant cells (Lee et al 2008). Our group have previously published a study on the design of NPs based on medium molecular weight (MMW) CS and incorporating a lysine-based surfactant with a different counterion (77KL, with lithium counterion) (Nogueira et al, 2013).…”

Recent Progress of Mussel‐Inspired Underwater Adhesives

“…[53,54] For example, the significantly increased acidity in the endosome can increase the efficiency of anticancer drug delivery via pH-initiated release of drugs from endocytosed drug carriers. [55] Catechol groups, as pH-responsive metal coordination groups, can respond to intracellular pH change for controlling drug release. On the basis of pH-responsive metal coordination, a series of catechol functional polymer conjugates of the anticancer drugs have been fabricated and used for pH-sensitive delivery to cancer cells.…”