Aptamer-liposome targeted nanotherapeutics for cancer therapy: Bibliometric analysis, recent developments and future perspectives

Abstract

As one of the leading causes of death worldwide, cancer has driven the advancement of targeted therapy toward greater precision and reduced off-target effects. Liposomes, with their biocompatibility, tunable properties, and clinical success, are among the most promising nanocarriers, yet their tumor-targeting specificity remains limited. Aptamer-functionalized liposomes provide a synergistic solution by combining selective aptamer-receptor recognition with efficient drug encapsulation, achieving enhanced tumor targeting and controlled release. Recent advances have expanded this platform toward multi-targeting, stimuli-responsive systems, and theranostic applications, thereby extending the potential of conventional liposomes. This review offers an integrated perspective on the structural design, internalization pathways, and therapeutic applications of aptamer-liposome systems across various cancers. Key barriers, including aptamer instability, scalable conjugation, and limited clinical translation, are critically discussed, alongside emerging strategies to address them. The convergence of aptamer targeting and liposomal delivery represents a transformative step toward next-generation nanotherapeutics, offering a paradigm shift in precision oncology by enabling personalized, selective, and multifunctional cancer therapy.

Keywords: Aptamer; Cancer therapy; Liposome; Targeted drug delivery.

Graphical abstract

Fig. 1

Schematic diagram of aptamer-functionalized liposomes designed for precision-targeted cancer therapy.

Fig. 2

Keyword co-occurrence temporal mapping analysis of published articles.

Fig. 3

Predicted secondary structures of representative aptamers generated using the Mfold software.

Fig. 4

Schematics of strategies for efficiently incorporating aptamers into liposomes, pre-conjugation (A), post-insertion (B) and post-conjugation (C).

Fig. 5

Schematic representation of internalization pathways of aptamers (A) clathrin-mediated endocytosis and (B) macropinosomes. (C) Uptake inhibition assay of Apt-PEG-LPs by different inhibitors. (D) Analysis of cellular uptake of Apt-PEG-LPs based on fluorescence intensity measurements. Adapted from Ara et al., 2014 [131]. Copyright 2014, Elsevier.

Fig. 6

(A) NK cell immunopotentiators-loaded nanoliposomes enhance ADCC effect for targeted therapy against HER2-positive breast cancer. (B) Photographs of excised tumors. (C) corresponding tumor weights from each treatment group (n = 5). (D) Proportion of Perforin-positive or granzyme B-positive rates in tumor-infiltrating NK cells. Adapted from Du et al., 2024 [141]. Copyright 2024, Springer Nature. (E) Schematic illustration of the synthesis of HApt-tFNA@DM1 (HTD), PEOz-erythrosome@HTD, and their proposed antitumor mechanism. (F) Tumor volume and body weight changes in SKBR3 tumor-bearing mice treated with different formulations (n = 5). Adapted from Ma et al., 2022 [109]. Copyright 2022, Wiley-VCH GmbH.

Fig. 7

Characterization and biological effects of Axl-LP-VD-CTA091 in EGFR-mutant NSCLC models. (A) Axl-LP-VD-CTA091 targets DTCs undergoing EMT to prevent EGFR TKI resistance. (B) Schematic of Axl-targeted liposomes co-loaded with VD and CTA091. (C, D) Confocal imaging and flow cytometry confirmed selective uptake and binding of Axl-targeted liposomes by H1975OR cells. (E, F) Treatment modulated EMT marker expression and enhanced osimertinib sensitivity. (G, H) In vivo imaging demonstrated tumor-selective biodistribution of Axl-LP formulations. (I–K) Axl-LP-VD-CTA091 suppressed tumor growth in an orthotopic xenograft model without significant toxicity. Adapted from Shaurova et al., 2023 [148]. Copyright 2023, Wiley-VCH GmbH.

Fig. 8

Specific binding (A) and cytotoxicity (B) of Dox-encapsulating aptamosomes to LNCaP prostate cancer cells. Adapted from Baek et al., 2014 [152]. Copyright 2014, Elsevier. (C) Schematic diagram of MDS@LA targeting PC-3 cells. (D) Fluorescence images and quantitative intensity analysis of the selective uptake of MDS@LA by PC-3, HELA, and 293T cells. (E) In vivo antitumor effect of MDS@LA. Adapted from Dai et al., 2025 [153].Copyright 2025, American Chemical Society.

Fig. 9

(A) The tumour weights of nude mice at the end of the administration cycle in BALB/C hormonal nude mice. (B) The tumour growth curves. (C) Results of biochemical indexes of the liver and kidney of tumour-bearing BALB/C nude mice in each group. Adapted from Zhang et al., 2025 [156]. Copyright 2025, Elsevier. (D) The schematic diagram shows the anti-HCC mechanism of CAP@CD133-D/X-Lip. Adapted from Kong et al., 2024 [106].Copyright 2024, Elsevier. (E) Schematic illustration of apigenin-encapsulated, PEGylated nanoliposomes functionalized with phosphorothioated amino-modified-AS1411 aptamer. Adapted from Dhara et al., 2023 [157]. Copyright 2023, Springer.

Fig. 10

MNPs/MANPs treatment downregulated NOTCH1 expression at both the mRNA (A) and protein (B) levels. (C) Representative tumor images from each group, along with tumor growth curves (D), tumor weight comparisons (E), and body weight monitoring during treatment (F). Adapted from Zhao et al., 2019 [161]. Copyright 2019, American Chemical Society.

Fig. 11

(A) Schematic illustration of DP-CLPs–PTX–siRNA nanocomplex. (B) In vivo fluorescence imaging of intracranial U251-CD133þ glioma tumor-bearing nude mice treated for 24 h with CLPs–PTX–survivin siRNA (B1) or DPCLPs–PTX–survivin siRNA (D1) liposomes, as well as corresponding dissected organs (A1 and C1). Adapted from Sun et al., 2018 [89].Copyright 2018, Taylor & Francis. (C) Schematic illustration of I&T@LipA synthesis. (D) Schematic illustration of the in vitro BBB model. (E) Fluorescence imaging of the bottom chamber of the transwell plate added with PBS, I&T@Lip, I&T@LipC, and I&T@LipA. (F) Quantitative data of body weights of mice and (G) Percent survival of mice in different groups of saline, I@LipA + L, T@LipA, and I&T@LipA + L. Adapted from Zeng et al., 2023 [163]. Copyright 2023, Springer Nature.

Fig. 12

(A) Preparation process and lipid composition of Lip@AUR-ACP-aptPD-L1. (B, C) Tumor volume progression during treatment and final tumor weight analysis across different groups. (D) Survival curves showing that combination therapy significantly prolongs overall survival. (E) Western blot analysis of key protein expression in tumor tissues. (F) Measurement of ATP and MMP-2 release in tumor tissues under various treatments. Adapted from Ren et al., 2024 [115]. Copyright 2024, Springer Nature. (G) Schematic illustration of nucleolin-targeted DOX and ICG co-loaded theranostic lipopolymersome for photothermal-chemotherapy of melanoma in vitro and in vivo. Adapted from Abbasi et al., 2024 [165]. Copyright 2024, Elsevier.