Progress and challenges towards targeted delivery of cancer therapeutics
Open accessAbstract
Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.
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A huge disparity in the EPR effect exists between tumor types, sizes, and sites, mostly associated with inconsistency in construction and function of tumor blood vessels.
“A huge disparity in the EPR effect exists between tumor types, sizes, and sites, mostly associated with inconsistency in the construction and function of tumor blood vessels [123].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [123]
In “Passive targeting and the EPR effect” (page unavailable), the paper describes EPR heterogeneity within and between tumors and links non-uniform delivery to variable endothelial gaps, permeability, and perfusion. It also reports differences among tumor types. The passages do not establish variation by tumor size or show that blood-vessel differences account for most of the disparity. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSeveral studies have demonstrated that only 0.1 to 0.2% of the injected dose is efficient against tumor cells and exhibits significant anticancer effects.
“Several studies have demonstrated that only 0.1 to 0.2% of the injected dose is efficient against tumor cells and exhibits significant anticancer effects [20,123,161].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [123]
In “Crossing physiological barriers > Passive targeting and the EPR effect” (page unavailable), the review reports that 0.2% of an injected dose of free paclitaxel reached tumors in one preclinical study. It does not report a 0.1–0.2% range or establish that this fraction reached tumor cells and produced significant anticancer effects; its reported median for nanocarriers reaching tumors is about 0.7%. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTranscytosis is a metabolically active process that necessitates endothelial cells to reorganize their cytoskeleton and cell membrane, involving vesicle formation transporting NPs through the cytoplasm.
“Transcytosis is a metabolically active process that necessities endothelial cells to reorganize their cytoskeleton and cell membrane, involving vesicle formation transporting NPs through the cytoplasm [123,162].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [123]
The ‘Active targeting has great potential and greater challenges’ section discusses nanocarrier endocytosis and intracellular trafficking in target cells, but not transcytosis across endothelial cells. Searches for transcytosis, metabolic activity, cytoskeletal reorganization, and vesicle formation found no passage in our copy addressing those attributed details. No page number was provided for the indexed passages. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Rosenblum, D., Joshi, N., Tao, W., Karp, J. M., & Peer, D.
- Affiliations
- Tel Aviv University (IL)
- Brigham and Women's Hospital (US)
- Corresponding author
- Karp, Jeffrey M.
- Peer, Dan
- Venue
- Nature Communications
- Published
- 2018-04-12
- Volume
- 9
- Issue
- 1
- Pages
- 1410-1410
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5897557
- OpenAlex
- W2796781998
- Cited by
- 2,220
- References
- 95
- Citations by year
- 2026: 191 · 2025: 268 · 2024: 228 · 2023: 288 · 2022: 321 · 2021: 340 · 2020: 332 · 2019: 202 · 2018: 49 · 2012: 1
- FWCI
- 15.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Prostate Cancer Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Israel Science Foundation (1178/16)
- Tel Aviv University
- National Institutes of Health (NIH-R01, R01‐grant)
- National Heart, Lung, and Blood Institute (R01HL095722)
- H2020 European Research Council (647410)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- targeted drug delivery, cancer therapeutics, nanocarriers, active targeting, passive targeting, clinical translation, nanomedicine
- MeSH terms
- Antineoplastic Agents, Drug Carriers, Drug Compounding, Humans, Neoplasms, Drug Approval, Nanomedicine, Nanoparticles, Molecular Targeted Therapy
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