---
title: "Directional coating of cell membranes preserves orientation and extends circulation of biomimetic"
id: "pubmed-42508509"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42508509"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42508509/"
doi: "10.1016/j.ijpharm.2026.127241"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Directional coating of cell membranes preserves orientation and extends circulation of biomimetic
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42508509
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42508509/)
- **DOI:** [10.1016/j.ijpharm.2026.127241](https://doi.org/10.1016%2Fj.ijpharm.2026.127241)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Cell membrane–coated nanocarriers aim to reduce drug toxicity and prolong systemic circulation by using natural cell membranes as a biomimetic shell. - A major unresolved problem is membrane inside-out inversion during coating, which can impair native functions such as homologous targeting and long circulation. - The authors developed a **directional coating** strategy by screening a peptide that specifically binds **phosphatidylserine (PS)** on the inner leaflet of cell membranes and attaching that peptide to the surface of drug-loaded nanoparticles to guide correct membrane orientation. - The approach was applied to engineer red blood cell membrane (**RBCm**)–coated bufalin liposomes (BF/Lip-Pep@RBC), preserving outward display of **CD47** and internalization of PS. - Compared with non-directional coating controls, BF/Lip-Pep@RBC reduced macrophage uptake by 79.76% and extended circulation half-life by 2.24-fold. - In a breast cancer model, the directional RBCm-coated BF liposomes showed potent antitumor efficacy with acceptable biosafety as reported in the source. - The strategy addresses the often-overlooked issue of membrane orientation loss and is presented as broadly applicable and scalable for designing functionally intact cell membrane–coated nanomedicines. - Keywords highlighted in the source include **Breast cancer**, **Bufalin**, **Directional coating**, **Long circulation**, and **Red blood cell membrane**.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 27. # Directional coating of cell membranes preserves native orientation and prolongs circulation of biomimetic nanocarriers for tumor therapy [Weiying Huo](https://pubmed.ncbi.nlm.nih.gov/?term=Huo+W&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yutong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Gongjia Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+G&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yi Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yiming Huo](https://pubmed.ncbi.nlm.nih.gov/?term=Huo+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Jiezhong Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+J&cauthor_id=42508509)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-2 "Department of Psychology, School of Social Development and Public Policy, Fudan University, Shanghai 200433, China."), [Fei Qin](https://pubmed.ncbi.nlm.nih.gov/?term=Qin+F&cauthor_id=42508509)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-3 "Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou 510515, China."), [Bing Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+B&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Zhipeng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Z&cauthor_id=42508509)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-4 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: czpcpu2000@hotmail.com."), [Yutong Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42508509)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#full-view-affiliation-5 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wangyutong@njucm.edu.cn.") Affiliations Expand ### Affiliations * 1 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 2 Department of Psychology, School of Social Development and Public Policy, Fudan University, Shanghai 200433, China. * 3 Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou 510515, China. * 4 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: czpcpu2000@hotmail.com. * 5 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wangyutong@njucm.edu.cn. * PMID: **42508509** * DOI: [ 10.1016/j.ijpharm.2026.127241 ](https://doi.org/10.1016/j.ijpharm.2026.127241) Item in Clipboard # Directional coating of cell membranes preserves native orientation and prolongs circulation of biomimetic nanocarriers for tumor therapy Weiying Huo et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42508509/) . 2026 Sep 5:702:127241. doi: 10.1016/j.ijpharm.2026.127241. Epub 2026 Jul 27. ### Authors [Weiying Huo](https://pubmed.ncbi.nlm.nih.gov/?term=Huo+W&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yutong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Gongjia Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+G&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yi Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yiming Huo](https://pubmed.ncbi.nlm.nih.gov/?term=Huo+Y&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Jiezhong Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+J&cauthor_id=42508509)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-2 "Department of Psychology, School of Social Development and Public Policy, Fudan University, Shanghai 200433, China."), [Fei Qin](https://pubmed.ncbi.nlm.nih.gov/?term=Qin+F&cauthor_id=42508509)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-3 "Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou 510515, China."), [Bing Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+B&cauthor_id=42508509)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-1 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Zhipeng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Z&cauthor_id=42508509)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-4 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: czpcpu2000@hotmail.com."), [Yutong Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42508509)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42508509/#short-view-affiliation-5 "Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wangyutong@njucm.edu.cn.") ### Affiliations * 1 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 2 Department of Psychology, School of Social Development and Public Policy, Fudan University, Shanghai 200433, China. * 3 Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou 510515, China. * 4 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: czpcpu2000@hotmail.com. * 5 Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wangyutong@njucm.edu.cn. * PMID: **42508509** * DOI: [ 10.1016/j.ijpharm.2026.127241 ](https://doi.org/10.1016/j.ijpharm.2026.127241) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Cell membrane biomimetic delivery system can reduce the toxicity of encapsulated drugs and prolong systemic circulation. However, current studies have shown that cell membrane often undergo inside-out inversion during the coating process, which may weaken or impair their intrinsic functional properties, such as homologous targeting and long circulation in vivo. To address this, we developed a simple and effective directional membrane coating strategy by screening a peptide that specifically targets phosphatidylserine (PS) on the inner side of the cell membrane and modifying it onto the surface of drug-loaded nanocarriers. This approach preserves the native membrane orientation throughout the coating process. Using this strategy, we engineered red blood cell membrane (RBCm) directional coating bufalin (BF) liposomes (BF/Lip-Pep@RBC). The resulting nanocarrier retained CD47 outward display and PS internalization, reduced macrophage uptake by 79.76%, and extended circulation half-life by 2.24-fold compared to non-directional coating controls. In a breast cancer model, BF/Lip-Pep@RBC exhibited potent antitumor efficacy with favorable biosafety. By resolving the critical and long-overlooked issue of membrane orientation loss, this directional coating strategy establishes a broadly applicable and scalable platform for the rational design of functionally intact cell membrane-coated nanomedicines. **Keywords:** Breast cancer; Bufalin; Directional coating; Long circulation; Red blood cell membrane. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy. ](https://pubmed.ncbi.nlm.nih.gov/34391438/) Zhang Y, Xia Q, Wu T, He Z, Li Y, Li Z, Hou X, He Y, Ruan S, Wang Z, Sun J, Feng N.Zhang Y, et al.J Nanobiotechnology. 2021 Aug 14;19(1):245. doi: 10.1186/s12951-021-00977-3.J Nanobiotechnology. 2021.PMID: 34391438Free PMC article. * [ Tumor cell membrane-camouflaged biomimetic liposomes for targeted delivery of phytosphingosine with enhanced anti-lung cancer activity. ](https://pubmed.ncbi.nlm.nih.gov/42296942/) Fang L, Deng R, Yu S, Xue R, Ma Z, Xia L, Li J.Fang L, et al.Colloids Surf B Biointerfaces. 2026 Nov;267:115894. doi: 10.1016/j.colsurfb.2026.115894. Epub 2026 Jun 12.Colloids Surf B Biointerfaces. 2026.PMID: 42296942 * [ ROS-Responsive Biomimetic Nanocomplexes of Liposomes and Macrophage-Derived Exosomes for Combination Breast Cancer Therapy. ](https://pubmed.ncbi.nlm.nih.gov/40297405/) Xu M, Bai L, Sun M, Yan X, Xiong Y, Wang Y, Guo Y, Liu X, Yu L, Zhong X, Ran M, Wang B, Tang Y, Lee RJ, Xie J.Xu M, et al.Int J Nanomedicine. 2025 Apr 24;20:5161-5180. doi: 10.2147/IJN.S514375. eCollection 2025.Int J Nanomedicine. 2025.PMID: 40297405Free PMC article. * [ Biomimetic Nanoparticles for Targeted and Efficient Cancer Therapy: Progress, Challenges and Perspectives. ](https://pubmed.ncbi.nlm.nih.gov/41768394/) Kumar T, Thakur N, Simran, Prusti AK, Kumar R, Kaushik A, Kumar A.Kumar T, et al.Int J Nanomedicine. 2026 Feb 24;21:579622. doi: 10.2147/IJN.S579622. eCollection 2026.Int J Nanomedicine. 2026.PMID: 41768394Free PMC article.Review. * [ Biomimetic nanocarriers for targeted therapy of colorectal cancer. ](https://pubmed.ncbi.nlm.nih.gov/41042160/) Pathak S, Bera R, Sharma A, Kakkar D, Kurmi BD, Srivasatava P, Ghosh M, Sharma N.Pathak S, et al.Expert Opin Drug Deliv. 2025 Dec;22(12):1959-1975. d
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