ArticleJournal of controlled release : official journal of the Controlled Release Society2019
Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review.Frontiers in bioengineering and biotechnology · 2023Pooled it
- "Alkaline-Hammer Strategy" Breaks Acidic and Stromal Barriers to Induce Alkaliptosis and Enhance Immunotherapy in Pancreatic Cancer.Angewandte Chemie (International ed. in English) · 2026Article
- Mitochondrial preservation through the PKA-DRP1 axis empowers natural killer cells to resist acidic stress and retain cytotoxicity.Cell communication and signaling : CCS · 2026Article
- Targeting lactic acidosis in the tumor microenvironment: Enhancing TACE efficacy in hepatocellular carcinoma.Liver research (Beijing, China) · 2025Review
- Photoacoustic Chemical Imaging of Tumor Microenvironment pH for Prediction of Chemotherapeutic Efficacy in Breast Cancer.Nano letters · 2025Article
- Harnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective.The FEBS journal · 2025Review
- Recent advances of anti-tumor nano-strategies via overturning pH gradient: alkalization and acidification.Journal of nanobiotechnology · 2025Review
- Microenvironmental alkalization promotes the therapeutic effects of MSLN-CAR-T cells.Journal for immunotherapy of cancer · 2024Article
- Biochemical hallmarks-targeting antineoplastic nanotherapeutics.Bioactive materials · 2024Review
- Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy.Asian journal of pharmaceutical sciences · 2024Article
- Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model.Cancers · 2023Article
- Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment.Asian journal of pharmaceutical sciences · 2023Article
- Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Effects of preoperative bicarbonate and lactate levels on short-term outcomes and prognosis in elderly patients with colorectal cancer.BMC surgery · 2023Article
- Mn-based cGAS-STING activation for tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis.Journal of personalized medicine · 2023Review
- Advances in nanomaterial-based targeted drug delivery systems.Frontiers in bioengineering and biotechnology · 2023Review
- Precise delivery of doxorubicin and imiquimod through pH-responsive tumor microenvironment-active targeting micelles for chemo- and immunotherapy.Materials today. Bio · 2022Article
- Freeze-Dissolving Method: A Fast Green Technology for Producing Nanoparticles and Ultrafine Powder.ACS sustainable chemistry & engineering · 2022Article
- Tumor Microenvironment Modulating Functional Nanoparticles for Effective Cancer Treatments.Tissue engineering and regenerative medicine · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Acidic pH in the tumor microenvironment is associated with cancer metabolism and creates a physiological barrier that prevents from drugs to penetrate cells. Specifically, ionizable weak-base drugs, such as doxorubicin, freely permeate membranes in their uncharged form, however, in the acidic tumor microenvironment these drugs become charged and their cellular permeability is retarded. In this study, 100-nm liposomes loaded with sodium bicarbonate were used as adjuvants to elevate the tumor pH. Combined treatment of triple-negative breast cancer cells (4T1) with doxorubicin and sodium-bicarbonate enhanced drug uptake and increased its anti-cancer activity. In vivo, mice bearing orthotropic 4T1 breast cancer tumors were administered either liposomal or free bicarbonate intravenously. 3.7 ± 0.3% of the injected liposomal dose was detected in the tumor after twenty-four hours, compared to 0.17% ± 0.04% in the group injected free non-liposomal bicarbonate, a 21-fold increase. Analyzing nanoparticle biodistribution within the tumor tissue revealed that 93% of the PEGylated liposomes accumulated in the extracellular matrix, while 7% were detected intracellularly. Mice administered bicarbonate-loaded liposomes reached an intra-tumor pH value of 7.38 ± 0.04. Treating tumors with liposomal bicarbonate combined with a sub-therapeutic dose of doxorubicin achieved an improved therapeutic outcome, compared to mice treated with doxorubicin or bicarbonate alone. Interestingly, analysis of the tumor microenvironment demonstrated an increase in immune cell' population (T-cell, B-cell and macrophages) in tumors treated with liposomal bicarbonate. This study demonstrates that targeting metabolic adjuvants with nanoparticles to the tumor microenvironment can enhance anticancer drug activity and improve treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.