Forefronts and hotspots evolution of the nanomaterial software in anti-tumor immunotherapy: a scientometric evaluation | Journal of Nanobiotechnology

January 15, 2024

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Basic overview

A complete of 34 international locations revealed related literature on antitumor nano-immunotherapy (Fig. 1A, Extra file 7: Desk S2). The highest six international locations with the most important variety of publications had been China (208), the US (82), South Korea (21), Iran (17), India (17) and Japan (13) (Fig. 1B). The nation of related paperwork was primarily based on the nation of the corresponding creator and the primary creator. The variety of research on antitumor nano-immunotherapy has grown exponentially in recent times, and we speculated that the expansion charge of associated literature would nonetheless improve within the subsequent few years (Fig. 1C). Along with the primary creator and the corresponding creator, each creator contributed rather a lot to the paper. Due to this fact, we utterly agreed along with your solutions. We included the complete authors of the article and additional counted the full variety of authors in every nation to guage the contribution of the nation (Extra file 1: Fig. S1, Extra file 7: Desk S3). Extra file 2: Fig. S2 Confirmed the highest six international locations contributing to this discipline. Extra file 3: Fig. S3 confirmed the cooperation between completely different international locations.

Ten establishments have revealed greater than 20 related papers: Sichuan College (Sichuan Province, China, 30), Taipei Medical College (Taiwan Province, China, 28), Wuhan College (Hubei Province, China, 27), Nanjing College (Jiangsu Province, China, 26), North Carolina State College (North Carolina, USA, 25), Mashhad College of Medical Sciences (Reza Khorasan, Iran, 25), Soochow College (Jiangsu, China, 23), College of California, Los Angeles (California, USA, 22), Shanghai Jiaotong College (Shanghai, China, 21), South China College of Know-how (Guangdong, China, 21) (Fig. 1D). We additionally chosen the affiliated establishment of the primary corresponding creator for the follow-up evaluation (Extra file 4: Desk S4). As quite a few completely different establishments might exist in a single article, we thought the affiliated establishment of the primary corresponding creator could possibly be most consultant. The full variety of citations of related researches in China (4504) and the US (4282) had been far forward of different international locations. The common variety of citations within the Spanish literature was 133.8, rating firmly within the first place. In the meantime, the common variety of citations the US was 53.5, and that of China was solely 21.2 (Fig. 1E).

Amongst all related information, the full variety of authors of experimental articles (8.61) was considerably bigger than that of evaluate literature (5.05) (Fig. 2A). The variety of references within the evaluate literatures (156.8) was a lot larger than that within the experimental papers (56.77) (Fig. 2B). Research with greater than 20 citations had extra references (Fig. 2C). Each experimental articles and evaluate articles have elevated quickly in recent times, and the full quantity and progress charge of experimental articles are larger than that of evaluate literatures (Fig. 2D). Within the related articles revealed in China and the US, the variety of experimental articles was about twice that of evaluate literature. Nonetheless, evaluate literatures accounted for the overwhelming majority of articles revealed in different international locations (Fig. 2E). For the above six international locations with the most important variety of publications, about 38% of the articles revealed in the US had been accomplished by a number of international locations, whereas the proportion of articles revealed in Iran was solely 12% (Fig. 2F).

Journal correlation evaluation

The journal co-citation community confirmed that papers within the discipline of anti-tumor nano-immunotherapy was primarily revealed in two forms of journals (Fig. 3A). The purple color represents journals of supplies science, whereas the blue elements had been primarily medical journals. We discovered that the co-citations between the 2 clusters had been plentiful, which was in line with the theme of nanomaterials for tumor immunotherapy. Prior to now 5 years, the 2 journals, Journal of Managed Launch and Biomaterials, have seen the quickest progress within the variety of articles revealed in associated fields (Fig. 3B). Determine 3C exhibits that the Journal of Managed Launch revealed by Netherlands revealed the best variety of information on the topic (a complete of 28 revealed information, 2021 IF = 11.467), adopted by Biomaterials revealed by Netherlands (26 publications in whole, 2021 IF = 15.304), and Acta Biomaterialia revealed by England (a complete of 16 publications, 2021 IF = 10.633). There have been three journals with the fourth largest variety of publications, every publishing 11 articles, particularly Theranostics (2021 IF = 11.6), Superior Supplies (2021 IF = 32.086), and ACS Nano (2021 IF = 18.027). It’s price mentioning that the highest 20 journals by publication quantity belonged to the Q1 division (2021 JIF quartile), and the impression issue of every of the top-ranked journals was above 10. Due to this fact, it may be concluded that the thought of antitumor nano-immunotherapy is mostly acknowledged by high-quality journals. However, the highest 5 journals cited articles underneath research are: Biomaterials, ACS Nano, Journal of Managed Launch, Superior Supplies, Nature Communications (Fig. 3D). The highest 20 journals included many prime journals within the business, similar to Nature, Science, Cell, Superior Supplies, Nature Critiques Immunology, Nature Nanotechnology, and many others. This displays that the theoretical basis of antitumor nano-immunotherapy was stable.

Creator associated evaluation

We calculated the H index and the citations for various authors in articles related to this filed, and all analyses had been carried out solely within the 443 included articles. There are numerous consultants and students majoring within the discipline of antitumor nano-immunotherapy. A complete of 2571 authors, averaging 7.41 authors per article contributed to information underneath research. Amongst them, the highest 3 authors had been LIU Y (15 papers), HUANG L (13 papers), and WANG Y (12 papers) (Fig. 4A). The highest three authors with the best native H-index had been HUANG L (11), WANG C (9), and LIU Y (6) (Fig. 4B). The highest three authors cited most by native literature had been HUANG L (48), LIU Y (30), LIU XS (29) (Fig. 4C). The warmth map of the annual publication quantity of the highest 20 authors is proven in Fig. 6D. The creator co-citation community is proven in Fig. 6E. It may be seen that the important thing authors within the discipline of nanomaterials utilized to tumor immunotherapy included Prof. Yang Liu (Nankai College, China), Prof. Leaf Huang (College of North Carolina at Chapel Hill, USA) and Prof. Chao Wang (Soochow College, China).

Key phrases correlation evaluation

The cloud map of key phrases (Fig. 5A) exhibits that dendritic cells, supply, most cancers, T cells, immunotherapy, and photodynamic remedy had been the important thing analysis instructions for the applying of nanomaterials in tumor immunotherapy. The key phrases density map (Extra file 4: Fig. S4) confirmed that along with the above key phrases, immune checkpoint blockade, chemotherapy, tumor microenvironment, immune response, and many others. had been additionally scorching analysis matters in associated fields. The highest 5 key phrases with the best frequency of incidence are (Fig. 5C): nanoparticles (87), dendritic cells (83), supply (68), most cancers (62), remedy (54). The annual time period frequency line chart of key phrases included within the literature confirmed that the utilization of above key phrases has grown quickly in recent times (Fig. 5D). By means of the correlation warmth map (Extra file 5: Fig. S5), we concluded that immunotherapy is most carefully associated to key phrases, similar to immune checkpoint blockade (correlation coefficient = 0.71), photodynamic remedy (correlation coefficient = 0.65), photothermal remedy (correlation coefficient = 0.57), T cells (correlation coefficient = 0.58), tumor-associated macrophages (correlation coefficient = 0.52), tumor microenvironment (correlation coefficient = 0.47), immunogenic cell demise (correlation coefficient = 0.43), and many others. As well as, dendritic cells had been carefully associated to vaccine (correlation coefficient = 0.46), and photodynamic remedy was carefully associated to checkpoint blockade (correlation coefficient = 0.33).

The annual major key phrases evolution chart reveals (Fig. 5B) that the primary key phrases in 2022 was autophagy; 2021 included immunogenic cell demise, tumor-associated macrophages, focused supply, pure killer cells, hypoxia, antitumor-activity, antibody and in 2020 included supply, T cells, and many others. The primary key phrases in 2019 included dendritic cells, drug supply, regulatory T cells, and many others. The sooner key phrases included vaccine supply, antigen cross-presentation, cd4(+) t-cells, and many others.

The co-occurrence evaluation of key phrases exhibits (Fig. 6A) that key phrases had been divided into 12 clusters, represented by completely different colours. Amongst them, Modularity Q = 0.5624 and Weighted Imply Silhouette = 0.7886 indicated that the clustering outcomes had been convincing sufficient. We discovered that the consultant phrases of the primary three clusters had been: antigen, most cancers immunotherapy, dendritic cells. Primarily based on the above clustering, we additional obtained an evolution timeline of key phrases clustering (Fig. 6B). As proven in Fig. 6C, some research have been enduring in recent times, similar to drug-delivery and dendritic cells.

Strategic diagram of the sub-period (Fig. 6D) confirmed that regulatory T cells, tumor microenvironment, immune checkpoint blockade, drug-delivery, photodynamic remedy, photothermal remedy, tumor-associated macrophages, and many others. situated within the Motor Themes quadrant, indicating that the above key phrases had been the core theme with excessive maturity. As well as, dendritic cells, vaccine, and T cells had been situated within the Fundamental Themes quadrant, which demonstrated that the above key phrases had been essential however the present analysis was not sufficient, so the above matters might grow to be analysis hotspots or future improvement developments.

Nation associated evaluation

In reality, cooperation amongst authors of various international locations on this discipline is quite common, with the proportion of worldwide cooperation within the included literature being as excessive as 28.67%. As a consultant of developed international locations, the US has cooperated with plenty of developed and creating international locations, similar to China, South Korea, India, Egypt, Saudi Arabia, Argentina, Iran, Israel, Spain, Portugal and so forth. America and China, because the leaders on this discipline, have maintained shut cooperation with the remainder of the world, which is especially essential to the frequent progress of world drugs. As well as, creating international locations similar to India, Iran, Egypt, Saudi Arabia and Romania additionally play an more and more essential position on this discipline. With the joint efforts of each developed and creating international locations, this discipline will transfer in direction of a greater future.

The nation of the doc was primarily based on the nation of the corresponding creator. If there have been corresponding authors affiliated with establishments in numerous international locations, the nation of the primary creator shall prevail. Researches within the discipline of antitumor nano-immunotherapy had been primarily carried out in China and the US. The remainder of the international locations revealed much less papers and weren’t additional analyzed. The warmth map of the variety of papers revealed by every province in China (Fig. 7A) confirmed that the provinces of associated fields had been primarily distributed within the southeastern provinces, of which Jiangsu Province (31), Shanghai (22), and Guangdong Province (17) contributed essentially the most. The warmth map of the variety of publications by provinces in the US (Fig. 7E) confirmed that the publications of associated fields had been primarily distributed on the east coast, of which North Carolina (16), Michigan (9), and California (9) contributed essentially the most.

Within the discipline of antitumor nano-immunotherapy, analysis hotspots shared by China and the US included dendritic cells, supply, T cells, and mixture. There have been some distinctive analysis hotspots in China: immune checkpoint blockade, photodynamic remedy, and immunogenic cell demise. The US-specific analysis hotspot was expression (Fig. 7B, F).

The variety of articles associated to China and the US has grown quickly in 2022. Amongst them, the variety of publications in China confirmed an exponential rise between 2013 and 2021, whereas the US confirmed a linear progress (Fig. 7C, G). The highest 5 establishments in China for publishing papers included SICHUAN UNIV, NANJING UNIV, TAIPEI MED UNIV, WUHAN UNIV, and SOOCHOW UNIV. The highest 5 establishments in the US included UNIV N CAROLINA, UNIV CALIF LOS ANGELES, UNIV MICHIGAN, UNIV PITTSBURGH, and JOHNS HOPKINS UNIV (Fig. 7D, H).

Adopting IF as an analysis indicator, the standard of papers in China and the US had been related. The common IF of American articles was 11.84, whereas the common IF of Chinese language articles was 10.74, and there was no vital statistical distinction between the 2 (Fig. 7I). As well as, there was additionally no statistical distinction in IF between evaluate articles and experimental articles in China and the US (Fig. 7J).

Correlation evaluation of key papers

The appliance of nanomaterials in tumor immunotherapy has acquired intensive consideration and citations. Amongst them, Pérez-Herrero E [28] summarized the benefits and limitations of many nanocarriers loaded with completely different chemotherapeutic medicine in tumor remedy. The research was cited 752 occasions in whole (Fig. 8B) and 20 occasions in native literature (Fig. 8A). On the similar time, the variety of annual citations of this analysis have continued to develop in recent times (Fig. 8C). Yang G et al. [29] developed a Hole MnO₂-based nano-platform H-MnO₂-PEG/C&D mixed with anti-PD-L1, which may activate tumor immunity in mice and considerably inhibit major tumors and metastatic tumors. The paper has been cited 698 occasions in whole (Fig. 8B), 224 occasions final yr alone, and the diploma of consideration has elevated yr by yr (Fig. 8C).

Lu J et al. [30] designed a nano-platform OX/IND-MSNP, during which phospholipid bilayer-wrapped mesoporous silica nanoparticles had been concurrently loaded with oxaliplatin and immunostimulatory medicine. This nanoparticle may successfully induce tumor immunogenic cell demise (ICD) and set off the antigen presentation of dendritic cells, additional inducing the activation of T cells and tumor immune reminiscence. Lu J’s paper was cited 26 occasions (Fig. 8A). Li SY et al. [31] constructed nanoparticles to ship CTLA-4 siRNA (NPsiCTLA-4) and confirmed the power of this siRNA supply system to enter T cells each in vitro and in vivo, eliminating the immunosuppression within the tumor microenvironment. Li SY’s paper was cited 18 occasions (Fig. 8A). As well as, there have been additionally wealthy quotation relationships between these key literatures (Fig. 8D).

Along with the articles talked about above, the next papers additionally ranked within the prime ten citations on this discipline. Jain RK [32] discovered that the tumor-associated hematological and lymphatic vasculature, fibroblasts, immune cells, and extracellular matrix had been irregular, which collectively created a hostile tumor microenvironment. Nonetheless, vascular normalization can convert the immunosuppressive tumor microenvironment into an immunoactivated tumor microenvironment, and enhance the efficacy of immunotherapy through rising blood move and oxygenation. Corbo C et al. [33] noticed that nanomaterials interacted with organic parts and surrounded with a protein corona (PC) whereas be injected in physiological environments similar to blood. This will set off an immune response and have an effect on the toxicity and concentrating on skill of the NP. Moon JJ et al. [34] reviewed the superior findings of the nanoparticle developments for immunotherapy and analysis. Nanomaterials used within the tumor microenvironment or in systemic lymph nodes confirmed satisfying potential. Furthermore, methods to actively goal most cancers therapeutic brokers to the tumor microenvironment utilizing immune cells themselves as supply automobiles had been additionally very attention-grabbing. Hamdy S et al. [35] reviewed the functions of poly (D, L-lactic-co-glycolic acid) nanoparticles (PLGA-NPs) in most cancers vaccine supply techniques. PLGA-NPs containing antigens or immunostimulatory molecules can’t solely actively goal DC, but in addition rescue impaired DC from tumor-induced immune suppression. Singh A et al. [36] raised an rising immunomodulation concept primarily based on hydrogel and scaffold, which may be completely utilized in a wide range of tumors. As well as, hydrogels and stents can even carry out effectively in ailments apart from the tumors, similar to continual infections and autoimmune ailments. Zhu G et al. [37] reviewed the vaccines for most cancers immunotherapy by synthetizing nanoparticles or naturally derived nanoparticles. Nanovaccines can successfully co-deliver immune-activating adjuvants and multiepitope antigens into lymphoid organs and antigen-presenting cells, fine-tuning the intracellular launch and cross-expression of the antigen by nano vaccine engineering. von Roemeling C et al. [38] found that as immunotherapy grew to become more and more essential in scientific oncology, the methods using the interactions between nanomaterials and numerous parts of the immune system supplied potentialities for exploring novel immune adjuvants to exert enhanced antitumor results.

Correlation evaluation of impression issue

Correlation evaluation confirmed that the impression issue of a research was positively correlated with the variety of citations (Fig. 9A) and the variety of references (Fig. 9B). The common variety of authors of papers with an impression issue above 10 was considerably bigger than that of papers with an impression issue of lower than 10 (Fig. 9C). The common impression issue of the experimental literature (IF = 10.36) was larger than that of the evaluate literature (IF = 9.04), nonetheless there was no statistical distinction between the 2 (P = 0.055) (Fig. 9D). The impression issue of articles revealed in recent times has improved considerably, as in contrast with that earlier than 2015 (Fig. 9E), and this was additionally thought-about to be associated to the general improve in impression issue.