Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Search and Study Selection
2.2. Data Analysis
2.3. Quality Assessment
3. Results
3.1. Overview of Included Studies
3.2. Types of NPs Used
3.3. Outcomes of pH-NPs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Inclusion Criteria | Exclusion Criteria |
---|---|
Experimental studies | Clinical studies |
Full text available in English | Full text not available/other language used |
Testing of pH-NPs in vitro and in vivo (animal model) | In vitro/in vivo only |
Descriptive data on type and synthesis of NPs | Type of NPs not named/method of synthesis not described |
Descriptive data on pH functionalization method | No detailed data on how the NPs were functionalized |
Data on animal model and malignant cell line used | No data on animal model/malignant cell line |
pH-NPs used to deliver chemotherapeutics | Other use of pH-NPs (e.g., tumor imaging, hyperthermia) |
Analysis of tumor uptake of pH-NPs and tumor regression | No data on tumoral response to pH-NPs |
Detailed description of methodology (is the method reproducible?) | Methods not reproducible based on given data (requiring supplemental data from authors) |
ARRIVE score ≥ 15 | ARRIVE score < 15 |
Summary of Studies Overview of Common Methods | ||
---|---|---|
Type/Method | No. of Studies | |
Type of NPs | Polymeric | 55 |
Lipid | 12 | |
MSN | 13 | |
Metallic | 11 | |
Other | 29 | |
pH Sensitization Method | pH-labile linkers | 70 |
pH-triggered structural changes | 35 | |
pH-triggered hydrophobic to hydrophilic transition | 8 | |
Other methods | 7 | |
Cancer Model | Breast malignant cell lines (4T1, MCF-7, MDA-MB-231) | 48 |
Cervical malignant cell lines (HeLA) | 8 | |
Lung malignant cell lines (A549) | 14 | |
Colorectal malignant cell lines (CT-26, HCT116, SW480) | 8 | |
Liver malignant cell lines (H22, HepG2, SMMC 7721) | 17 | |
Other | 25 | |
Types of Chemotherapeutics | Doxorubicin | 69 |
Paclitaxel | 9 | |
Other | 42 |
First Author | Publication Year | Structure of NPs | pH Sensitization Method | Tumor Type | Drug |
---|---|---|---|---|---|
Adeyemi [19] | 2019 | FA-chitosan-PEG-polyethylenimine | pH-triggered structural changes | KYSE 30 scuamos cell carcinoma | Endostatin |
Cao [21] | 2019 | TAT peptide-polyphosphoester | pH sensitive transactivator of transcription (TAT) | MDA-MB-231 breast carcinoma cell line | Doxorubicin |
Chen [23] | 2018 | lactobionic acid-chitosan-lipoic acid | pH-labile amide linkers | HepG2 liver cancer | Doxorubicin |
Chen [25] | 2020 | TPGS-HA polymer-PEG | hydrophobic to hydrophilic transition | PC3 prostate cancer | Docetaxel |
Cheng [30] | 2019 | Poly(ortho ester urethanes) copolymers | pH-labile borate ester linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Cheng [28] | 2018 | carboxymethyl chitosan | pH-labile hydrazone linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Cui [31] | 2017 | transferrin-PEG | pH-labile hydrazone linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Debele [32] | 2017 | PEG-methacrylamide-tocopheryl succinate-histidine | pH-labile imidazole linkers | HCT116 colon carcinoma | Doxorubicin |
Deng [33] | 2019 | PEG-methylpropenoic acid-glycerol-cinnamaldehyde | pH-labile cinnamylaldehyde linkers | 4T1 breast carcinoma cell line | Doxorubicin |
Du [36] | 2017 | PEG-PTTMA | PTTMA disassembly in acidic pH | HeLa cervival cancer | siRNA |
Fan [39] | 2017 | polyethylenimine-PEG | pH-labile borate ester linkers | 4T1 breast carcinoma cell line | siRNA |
Fang [40] | 2020 | chitosan-polysaccharide | pH-labile borate ester linkers | PANC-1 pancreatic cancer | Curcumin |
Feng [41] | 2020 | PEG-PAH-DMA | pH-triggered structural changes | A549 NSLC cell line | Paclitaxel |
Gao [44] | 2017 | poly (L-γ-glutamylcarbocistein-RBC membrane | pH-triggered structural changes | NCI-H460 cell line | Paclitaxel |
Gibbens-Bandala [45] | 2019 | PLGA-polyvinyl alcohol | hydrophobic to hydrophilic transition | MDA-MB-231 breast carcinoma cell line | Paclitaxel |
Gong [47] | 2018 | PEG-PPMT | hydrophobic to hydrophilic transition | CT-26 colon carcinoma | Docetaxel |
Guo [49] | 2018 | PBLG-Sericin | pH-labile carboxyl linkers | A549 NSLC cell line | Methotrexate |
Guo [51] | 2020 | DMA-PEG | pH-triggered structural changes | MCF-7 breast carcinoma cell line | Doxorubicin |
Hong [53] | 2019 | U11 peptide-PLGA | pH-triggered structural changes | A549 NSLC cell line | Doxorubicin and Curcumin |
Jin [57] | 2018 | PEI-PLA | pH-triggered structural changes | A549 NSLC cell line | Paclitaxel |
Jung [58] | 2020 | PBA | pH-labile borate ester linkers | MG glioblastoma | Doxorubicin |
Khan [61] | 2020 | PLGA | pH-triggered structural changes | MCF-7 breast carcinoma cell line | Doxorubicin |
Kou [64] | 2017 | lactose myristoyl carboxymethyl chitosan | pH-triggered structural changes | Huh-7 hepatocellular carcinoma | Adriamycin |
Lee [66] | 2018 | chitosan-PEG-acetyl histidine | pH-triggered structural changes | CT-26 Pulmonary Metastasis Model | Piperlongumine |
Li [70] | 2018 | DGL-PEG-Tat-KK-DMA | pH-labile amide linkers | HepG2 liver cancer | Doxorubicin |
Li [73] | 2020 | RGD-PEG-Arginine-SA | pH-labile hydrazone linkers | HN6 squamos cell carcinoma | GNA002 |
Li [75] | 2021 | PDA-HA | pH-labile PDA coating | 4T1 breast carcinoma cell line | Cisplatin |
Liu [79] | 2018 | polycarbonate-PEG | pH-labile acetal linkers | BT 474 breast carcinoma | Bortezomib |
Luo [87] | 2021 | PEG-TAT-HA | pH-triggered structural changes | H22 hepatocellular carcinoma | Disulfiram |
Mhatre [89] | 2021 | polydopamine | pH-triggered structural changes | MDA-MB-231 breast carcinoma cell line | Niclosamide |
Palanikumar [96] | 2020 | ATRAM-BSA-PLGA | pH-labile ester bonds | MCF-7 breast carcinoma cell line | Doxorubicin |
Qu [100] | 2018 | carboxymethyl chitosan | pH-labile phenylboronic acid pinacol ester | HepG2 liver cancer | Doxorubicin |
Quadir [101] | 2017 | PEG-PPLG | pH-labile amine linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Ray [102] | 2020 | PEG | pH-labile amine linkers | PANC-1 pancreatic cancer | Gemcitabine |
Saravankumar [103] | 2019 | APT-PLGA-PVP-AS1411 aptamet | pH-triggered structural changes | A549 NSLC cell line | Doxorubicin |
Shi [105] | 2018 | PEG-PLH | pH-labile PSD linker | A549 NSLC cell line | siRNA |
Shi [106] | 2021 | PEG-PLL-DMA | pH-labile amide linkers | A549 NSLC cell line | siRNA |
Soe [107] | 2019 | poloxamer-Tf-EDC-NHS | NR | MDA-MB-231 breast carcinoma cell line | Doxorubicin |
Su [108] | 2020 | PEG-PMT | pH-labile tioether linkers | Colon26 cell line | Docetaxel |
Wang [113] | 2017 | RGD-PLGA-PEG | pH-labile amine linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Wang [115] | 2018 | chitosan-graphene oxide | pH-triggered structural changes (less electrostatic interaction | HepG2 liver cancer | Doxorubicin |
Wei [118] | 2020 | PEG | pH-labile amine linkers (schiff base) | B16F10 melanoma | Doxorubicin |
Xiong [122] | 2019 | TPGS-PEG | pH-labile hydrazone linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
Xu [123] | 2018 | DTPA-PEG-DMA | pH labine amine linkers | PC3 prostate cancer | Doxorubicin |
Xu [124] | 2021 | chitosan | pH-labile ester linkers | HepG2 liver cancer | Doxorubicin |
Yadav [125] | 2020 | RGD-chitosan-Cy5.5 | pH-labile amine linkers | MDA-MB-231 breast carcinoma cell line | Raloxifene |
Yan [126] | 2017 | POEAd-galactose-LA | pH-labile ester linkers | HepG2 liver cancer | Doxorubicin |
Yang [127] | 2018 | glycol Chitosan-PDPA | hydrophobic to hydrophilic transition (PDPA) | MCF-7 breast carcinoma cell line | Paclitaxel |
Yu [128] | 2019 | PLGA-CPT-DMMA-PEI | pH-triggered structural changes | MCF-7 breast carcinoma cell line | Doxorubicin |
Zhang [129] | 2017 | TPGS-MSN | pH-labile ester linkers | SMMC 7721 hepatocellular carcinoma | Doxorubicin |
Zhang [131] | 2018 | DMA-Cystamine-PEG | pH-labile ester linkers | A549 NSLC cell line | Paclitaxel |
Zhou [138] | 2020 | polyphosphazene | pH-labile hydrazone linkers | HeLa cervival cancer | Doxorubicin |
First Author | Publication Year | Structure of NPs | pH Sensitization Method | Tumor Type | Drug |
---|---|---|---|---|---|
Chen [24] | 2020 | MSN-citraconic-poly-L-lisine | acid-labile disulfide linkers | 4T1 breast carcinoma cell line | Doxorubicin |
Cheng [27] | 2017 | Polydopamine-FA-PEG-MSN | pH-labile polydopamine coating | HeLa cervival cancer | Doxorubicin |
Ding [34] | 2020 | MSN-carboxymethyl chitin-GRP78 peptide | pH-labile thioketal linkers | H22 hepatocellular carcinoma | Doxorubicin |
Ding [35] | 2020 | MSN-lipidbilayer-TLS11a aptamer | pH-labile TAT peptide | 4T1 breast carcinoma cell line | Doxorubicin |
Kundu [65] | 2020 | MSN-FA | pH-labile PAA linker | MCF-7 breast carcinoma cell line | Umbelliferone |
Li [73] | 2020 | Gal-P123-MSN | pH-triggered structural changes (DC lipid) | Huh-7 hepatocellular carcinoma | Irinotecan |
Li [68] | 2017 | DM1-MSN-PDA | pH-labile PDA coating | SW480 colorectal cancer cell line | EpCAM |
Liao [76] | 2021 | Chitosan-MSN | pH-labile imidazole linkers | 4T1 breast carcinoma cell line | Doxorubicin |
Liu [80] | 2019 | MSN | pH-labile calcium carbonate | LNCaP-AI prostate carcinoma | Doxorubicin |
Mu [94] | 2017 | MSN-PLH-PEG | hydrophobic to hydrophilic transition | H22 hepatocellular carcinoma | Sorafenib |
Saroj [104] | 2018 | MSN | pH-labile PAA linker | PC3 prostate cancer | Bicalutamide |
Zhang [130] | 2017 | MSN-pH-responsive peptide | pH-responsive peptide | MCF-7 breast carcinoma cell line | Doxorubicin |
Zhao [136] | 2018 | MSN-TPGS | pH-labile ester linkers | MCF-7 breast carcinoma cell line | Doxorubicin |
First Author | Publication Year | Structure of NPs | pH Sensitization Method | Tumor Type | Drug |
---|---|---|---|---|---|
Aguilar [20] | 2021 | polycaffeic acid-FA-Au | pH-labile catechol-boronic acid linkers | SCC7 squamos cell carcinoma | Bortezomib |
Essawy [38] | 2020 | Au-hydrazine | pH-labile hydrazone linkers | HBPC oral carcinoma | Doxorubicin |
Guo [50] | 2018 | Au-Chitosan-AS1411 aptamer | pH-triggered structural changes | A549 lung cancer cell line | Methorexate |
Kumar [63] | 2020 | Au | pH-labile peptide linker (Lys-Phe-Gly) | BT 474 breast carcinoma | Doxorubicin |
Liu [81] | 2018 | Au-iron oxide-PEG | pH-labile oleic acid linkers | SGC-7901 gastric adenocarcinoma | Herceptin |
Mahalunkar [91] | 2019 | Au-PVP-FA | pH-triggered structural changes | MCF-7 breast carcinoma cell line | Curcumin |
Sun [110] | 2019 | Au-AS1411 aptamer | pH-triggered structural changes | HeLa cervival cancer | Doxorubicin |
First Author | Publication Year | Structure of NPs | pH Sensitization Method | Tumor Type | Drug |
---|---|---|---|---|---|
Juang [59] | 2019 | lipid-PEG | pH-labile imide linkers | HCT116 colon carcinoma | Irinotecan and microRNA |
Li [69] | 2017 | TF-PEG-GMS | pH-labile hydrazone linkers | A549/DTX lung cancer cell line | Docetaxel and Baicalin |
Li [71] | 2019 | LDL-OA | pH-labile hydrazone linkers | 4T1 breast carcinoma cell line | Doxorubicin |
Sun [111] | 2021 | DSPE-PEG | pH-triggered structural changes | LNCaP-AI prostate carcinoma | Doxorubicin |
Tan [112] | 2017 | PAA-OA | pH-labile oleic acid linkers | A549 NSLC cell line | Erlotinib |
Men [92] | 2020 | lipid-HA-PBAE | pH-triggered structural changes | A549 NSLC cell line | Doxorubicin |
Cavalcante [22] | 2021 | DSPE-PEG-OA | pH-labile oleic acid linkers | 4T1 breast carcinoma cell line | Doxorubicin |
Li [67] | 2017 | DSPE-PEG | pH-labile imine linkers | FTC-133 thyroid cancer | Doxorubicin |
Lo [85] | 2020 | DSPE-PEG | pH-labile oleic acid linkers | SAS squamos carcinoma cell line | Daunorubicin and Irinotecan |
Ma [90] | 2021 | DSPE-PEG | pH-triggered structural changes | HepG2 liver cancer | hydroxycamptothecin |
Pang [98] | 2020 | lipid-polymeric NPs | pH-labile dihydrazide linkers | A549 NSLC cell line | Erlotinib |
Xie [120] | 2018 | DSPE-PEG | pH-labile imine linkers | MCF-7 breast carcinoma cell line | Methotrexate |
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Morarasu, S.; Morarasu, B.C.; Ghiarasim, R.; Coroaba, A.; Tiron, C.; Iliescu, R.; Dimofte, G.-M. Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes. Gels 2022, 8, 232. https://doi.org/10.3390/gels8040232
Morarasu S, Morarasu BC, Ghiarasim R, Coroaba A, Tiron C, Iliescu R, Dimofte G-M. Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes. Gels. 2022; 8(4):232. https://doi.org/10.3390/gels8040232
Chicago/Turabian StyleMorarasu, Stefan, Bianca Codrina Morarasu, Razvan Ghiarasim, Adina Coroaba, Crina Tiron, Radu Iliescu, and Gabriel-Mihail Dimofte. 2022. "Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes" Gels 8, no. 4: 232. https://doi.org/10.3390/gels8040232