Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review

Abstract

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.

Keywords: bibliometrics; breast cancer; nanoparticle drug delivery systems; nanoparticles; visualization.

FIGURE 1

Epidemiological overview of breast cancer in the United States and in China.

FIGURE 2

(A) Increasing trend in publications and total citing articles (without self-citations); statistics evaluated using Pearson’s test; ** significant correlation coefficient. (B) Citing article (annual) trends on NDDSs in BC research from 2012 to 2022.

FIGURE 3

(A) Distribution of research on NDDSs in BC based on total worldwide publications. (B) Changing trend in the top 10 countries/regions based on annual publication 2012–2022. (C) Network visualization map of countries/regions. (D) Network visualization map of citation countries/regions produced by VOSviewer; line thickness denotes citation strength.

FIGURE 4

(A) Top ten institutions in the research field of NDDSs in BC. (B) Co-operation network between major institutions. In the visualization map (2012–2022), each node denotes one institution; lines between nodes represent co-citation relations. Different colours represent different times.

FIGURE 5

(A) Author co-authorship analysis generated using VOSviewer. In the network visualization, one cluster with the same colour indicates authors with a close relationship. (B) Collaborative network visualization of author citation analysis using VOSviewer; size of node shows the frequency of occurrence. Visualization map: each node represents an author. (C) Three-field plot represents the incoming and outgoing flows among top authors, affiliations, and countries contributing to research in the past 10 years.

FIGURE 6

(A) Trends of publications ranked in the top five journals 2012–2022. (B) Co-occurring subject categories network of NDDSs in BC research. (C) Dual-map overlay of journals reflected NDDSs in BC research 2012–2022.

FIGURE 7

(A) Visualization network and cluster of co-cited references. (B) Timeline view map of references’ co-cited analysis. (C) High-impact members of Cluster #0. (D) Top 45 references with citation bursts (sorted by year the burst began). Strength-value denotes the strength of citation bursts; red bars are the time of duration.

FIGURE 8

(A) Network map of keyword co-occurrence analysis using VOSviewer. Tightly linked keywords were assigned to one cluster of the same colour. Four clusters are listed, shown in red, chartreuse, blue, and yellow nodes. (B) Three-field plot showing incoming and outgoing flows among keywords, authors, and references (number of items: 20). (C1) Top 20 author keywords of highest frequency. (C2) Annual trend of word frequency in author keywords 2012–2022. (D) Timeline view map of keyword analysis. (E) Top 43 keywords with the strongest citation bursts.

FIGURE 9

Summary of tumour microenvironment (TME) of solid tumours and TME-related targets. TME of solid tumours possesses several particularities: hypoxia, acidic pH, reactive oxygen species (ROS), elevated ATP, excessive Zn²⁺, and a high level of glutathione (GSH). The researchers designed a series of NDDSs based on these particularities.

FIGURE 10

Types of nanoparticle-based drug delivery systems (NDDSs) used for BC therapy and their advantages.

FIGURE 11

Subtypes of BC and BS stages (Orrantia-Borunda et al., 2022). Top indicates five stages in BC, which is approved by Cancer.Net. The lower part shows another inclusion criteria. BC classification is luminal A, luminal B, HER2-positive, and triple-negative (four subtypes of BC), which are widely recognized based on molecular expression. The current clinical models for the classification of BC enjoy the advantages of several molecular markers, including miRNAs (let-7, miR-155, miR-150, and miR-153) and mutations (p53 and BRCA 1 and 2 genes).

FIGURE 12

Combination therapies for BC. To date, BC treatment includes surgery, chemotherapy, immunotherapy, endocrine therapy, targeted therapy, and radiation therapy.

FIGURE 13

Systemic delivery and biodistribution (A) Administration of nanomedicine, NDDSs reach the target position mainly through blood circulation. And the major organs responsible for nanoparticle excretion are the kidneys and the liver. (B) NP–protein interactions. The term “protein corona” (PC) is used to describe the layer that proteins form around NPs when placed in a biofluid. Proteins on the NP are always in the dynamic process of adsorption and desorption. With the prolongation of exposure time, the low affinity and high concentration of proteins close to the NP would be replaced by proteins with high affinity and low concentration, which rearrange at the surface of the particle and eventually form an irreversible stably hard corona composed of tightly bound proteins, while the replaced proteins absorbed on the outside form a reversible unsteadily soft corona consisting of loosely bound proteins [172]. (C) Blood circulation The process of NPs‘ distribution from the blood circulation to a specific organ/tissue/cell. Vascular extravasation into the TME which can be influenced by the perivascular TME, aberrant tumour vasculature. (D) Cellular uptake and intracellular trafficking-Scenarios of Carrier-Mediated Endosomal Escape and Subcellular Delivery of Cargos. Schematic of endocytosis and endosomal escape. Particles entered the cells via the endocytic pathway become entrapped in the visieles, the vesicles matured form early endosomes and late endosomes and eventually end up in the lysosome, the particles are effective by achieving the endosome escape. Alternatively, it is degraded by enzymes in the lysosome.

FIGURE 14

Data include papers published by PubMed and clinical trials registered at Clinicaltrials.gov. The number of publications indexed in PubMed >5,000; 465 studies were clinical trials (search was performed 1 July 2023) by querying Clinicaltrials.gov. The distribution of clinical trials with respect to the clinical trial phases demonstrated that the majority are in Phase Ⅱ (early Phase Ⅰ,5; Phase Ⅰ,97; Phase Ⅱ, 350; Phase Ⅲ, 72; Phase Ⅳ, 6, respectively). Seven nanomedicines have been approved for BC treatment.