Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes

Abstract

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines.

Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

“…These drug release data agree well with the vesicle degradation results ( Figure 4 b), where the vesicle size drastically decreased to 63 ± 23 nm after 12 h of incubation at pH = 3. These DOX release results also confirm that the vesicle degradation mainly occurs in the pH range from 4 to 3, which is characteristic of ester bond degradation ( Figure 4 b and Figure 5 a) [ 53 ].…”

Tumor acidity: From hallmark of cancer to target of treatment

“…( 91 , 92 ). It has recently been summarized that several types of pH-sensitive nanoparticle conjugates with paclitaxel, doxorubicin, or others enhance drug delivery and potentiate anticancer effects in various experimental cancer cell lines ( 93 ).…”

Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy

“…According to Ref. [ 78 ], 45.8% of published-by-now articles consider polymers to be a material for the fabrication of pH-responsive targeted delivery systems, 10% consider lipids, 12.5% consider mesoporous silica, and 6.7% consider metals ( Figure 3 ). However, current challenges push researchers to create hybrid carriers that combine properties of different materials; thus, the DDSs developed over the last 5 years are mostly multicomponent capsules or particles comprising inorganic compounds and specific polymers which endow them with multifunctionality.…”

“…Metal nanoparticles were the fourth most frequently used class of carriers among pH-responsive DDSs in the last 5 years [ 78 ]. Studies have shown that metal oxide nanoparticles (such as zinc oxide) exhibit high cancer cell selectivity, drug retention, and controlled release.…”