Polymer Nanoparticles for the Delivery of Anticancer Drugs, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 14226

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Guest Editor
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Interests: nano drug delivery systems; nucleic acid delivery; controlled release systems; targeted drug delivery
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Special Issue Information

Dear Colleagues,

Nanotechnology is at the commanding height of strategic technology in the 21st century, among which nanoparticles are revolutionizing the field of drug delivery, especially regarding cancer, their therapeutic effects in practical applications, though still being far from satisfactory on account of their poor water solubility and poor pharmacokinetics. Luckily, the booming nanocarriers have introduced bright prospects for gaining encouraging therapeutic outcomes, since they can be engineered to enhance the solubility and circulation time of drugs, as well as efficiently bringing drugs to cancer cells. Accordingly, a series of promising polymer nanoparticles are being developed for the delivery of anticancer drugs, such as PEG-PLA polymer micelles, PLGA nanoparticles, liposome, gold nanoparticles, etc. Additionally, advanced delivery systems have also been designed to deliver drugs specifically to the tumor site, based on their stimuli-responsive properties and cancer cell-specific markers. Nevertheless, the further exploration of identifying targeted molecules and designing nanocarriers is still worth continuing. Therefore, we would like to invite you to contribute both reviews and original articles highlighting recent progress in the development of polymer nanoparticles for the delivery of anticancer drugs, which will be published as part of a Special Issue entitled “Polymer Nanoparticles for the Delivery of Anticancer Drugs”. Main topics include, but are not limited to: polymer nanoparticles for chemotherapeutic drug delivery, chemotherapeutic drug and nucleic acid-based co-delivery, photosensitizer delivery, etc.

We look forward to receiving your contributions.

Dr. Wei Huang
Guest Editor

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Keywords

  • targeted nanoparticles
  • anticancer drug delivery
  • co-delivery system
  • stimuli-responsive
  • polymer nanoparticles
  • controlled release systems
  • solubilization

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Published Papers (7 papers)

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Research

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16 pages, 9268 KiB  
Article
Development of Novel Paclitaxel-Loaded ZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide Dimers and an Evaluation of Its Inhibitory Effect against Prostate Cancer Cells
by Heming Zhao, Liming Gong, Hao Wu, Chao Liu, Yanhong Liu, Congcong Xiao, Chenfei Liu, Liqing Chen, Mingji Jin, Zhonggao Gao, Youyan Guan and Wei Huang
Pharmaceutics 2023, 15(7), 1874; https://doi.org/10.3390/pharmaceutics15071874 - 3 Jul 2023
Cited by 5 | Viewed by 1638
Abstract
Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) [...] Read more.
Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer. Full article
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19 pages, 5641 KiB  
Article
A Gold Nanocage Probe Targeting Survivin for the Diagnosis of Pancreatic Cancer
by Lina Song, Shuai Ren, Yali Yue, Ying Tian and Zhongqiu Wang
Pharmaceutics 2023, 15(5), 1547; https://doi.org/10.3390/pharmaceutics15051547 - 19 May 2023
Cited by 1 | Viewed by 1535
Abstract
In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur–AuNC•Gd–Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and [...] Read more.
In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur–AuNC•Gd–Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and MR imaging agents, the gold cage is an outstanding platform. Furthermore, it has the potential to transport different drugs in the future, making it a unique carrier platform. The utilization of Sur–AuNC•Gd–Cy7 nanoprobes has proven to be an effective means of targeting and localizing survivin-positive BxPC-3 cells within their cytoplasm. By targeting survivin, an antiapoptotic gene, the Sur–AuNC•Gd–Cy7 nanoprobe was able to induce pro-apoptotic effects in BxPC-3 pancreatic cancer cells. The biocompatibility of AuNCs•Gd, AuNCs•Gd–Cy7 nanoparticles, and Sur–AuNC•Gd–Cy7 nanoprobes is evaluated through the hemolysis rate assay. The stability of AuNCs•Gd, AuNCs•Gd–Cy7 nanoparticles, and Sur–AuNC•Gd–Cy7 nanoprobes was evaluated by determining their hydrodynamic dimensions following storage in different pH solutions for a corresponding duration. Excellent biocompatibility and stability of the Sur–AuNC•Gd–Cy7 nanoprobes will facilitate their further utilization in vivo and in vitro. The surface-bound survivin plays a role in facilitating the Sur–AuNC•Gd–Cy7 nanoprobes’ ability to locate the BxPC-3 tumor. The probe was modified to incorporate Gd and Cy7, thereby enabling the simultaneous utilization of magnetic resonance imaging (MRI) and fluorescence imaging (FI) techniques. In vivo, the Sur–AuNC•Gd–Cy7 nanoprobes were found to effectively target and localize survivin-positive BxPC-3 tumors through the use of MRI and FI. After being injected via the caudal vein, the Sur–AuNC•Gd–Cy7 nanoprobes were found to accumulate effectively in an in situ pancreatic cancer model within 24 h. Furthermore, these nanoprobes were observed to be eliminated from the body through the kidneys within 72 h after a single injection. This characteristic is crucial for a diagnostic agent. Based on the aforementioned outcomes, the Sur–AuNC•Gd–Cy7 nanoprobes have significant potential advantages for the theranostic treatment of pancreatic cancer. This nanoprobe possesses distinctive characteristics, such as advanced imaging abilities and specific drug delivery, which offer the possibility of enhancing the precision of diagnosis and efficacy of treatment for this destructive illness. Full article
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13 pages, 3928 KiB  
Article
Cinchonain Ia Shows Promising Antitumor Effects in Combination with L-Asparaginase-Loaded Nanoliposomes
by Thi Nga Nguyen, Thi Phuong Do, Thi Cuc Nguyen, Ha Phuong Trieu, Thi Giang An Nguyen and Thi Thao Do
Pharmaceutics 2023, 15(5), 1537; https://doi.org/10.3390/pharmaceutics15051537 - 19 May 2023
Cited by 1 | Viewed by 1256
Abstract
Cancer is among the leading causes of death worldwide, with no effective and safe treatment to date. This study is the first to co-conjugate the natural compound cinchonain Ia, which has promising anti-inflammatory activity, and L-asparaginase (ASNase), which has anticancer potential, to manufacture [...] Read more.
Cancer is among the leading causes of death worldwide, with no effective and safe treatment to date. This study is the first to co-conjugate the natural compound cinchonain Ia, which has promising anti-inflammatory activity, and L-asparaginase (ASNase), which has anticancer potential, to manufacture nanoliposomal particles (CALs). The CAL nanoliposomal complex had a mean size of approximately 118.7 nm, a zeta potential of −47.00 mV, and a polydispersity index (PDI) of 0.120. ASNase and cinchonain Ia were encapsulated into liposomes with approximately 93.75% and 98.53% efficiency, respectively. The CAL complex presented strong synergistic anticancer potency, with a combination index (CI) < 0.32 in two-dimensional culture and 0.44 in a three-dimensional model, as tested on NTERA-2 cancer stem cells. Importantly, the CAL nanoparticles demonstrated outstanding antiproliferative efficiency on cell growth in NTERA-2 cell spheroids, with greater than 30- and 2.5-fold increases in cytotoxic activity compared to either cinchonain Ia or ASNase liposomes, respectively. CALs also presented extremely enhanced antitumor effects, reaching approximately 62.49% tumor growth inhibition. Tumorized mice under CALs treatment showed a survival rate of 100%, compared to 31.2% in the untreated control group (p < 0.01), after 28 days of the experiment. Thus, CALs may represent an effective material for anticancer drug development. Full article
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12 pages, 1343 KiB  
Article
Design and Characterization of a Novel Venetoclax-Zanubrutinib Nano-Combination for Enhancing Leukemic Cell Uptake and Long-Acting Plasma Exposure
by James Griffin, Yan Wu, Qingxin Mu, Xinyan Li and Rodney J. Y. Ho
Pharmaceutics 2023, 15(3), 1016; https://doi.org/10.3390/pharmaceutics15031016 - 22 Mar 2023
Viewed by 1669
Abstract
Leukemia remains incurable partly due to difficulties in reaching and maintaining therapeutic drug concentrations in the target tissues and cells. Next-generation drugs targeted to multiple cell checkpoints, including the orally active venetoclax (Bcl-2 target) and zanubrutinib (BTK target), are effective and have improved [...] Read more.
Leukemia remains incurable partly due to difficulties in reaching and maintaining therapeutic drug concentrations in the target tissues and cells. Next-generation drugs targeted to multiple cell checkpoints, including the orally active venetoclax (Bcl-2 target) and zanubrutinib (BTK target), are effective and have improved safety and tolerability compared to conventional, nontargeted chemotherapies. However, dosing with a single agent frequently leads to drug resistance; asynchronous coverage due to the peak-and-trough time-course of two or more oral drugs has prevented drug combinations from simultaneously knocking out the respective drugs’ targets for sustained leukemia suppression. Higher doses of the drugs may potentially overcome asynchronous drug exposure in leukemic cells by saturating target occupancy, but higher doses often cause dose-limiting toxicities. To synchronize multiple drug target knockout, we have developed and characterized a drug combination nanoparticle (DcNP), which enables the transformation of two short-acting, orally active leukemic drugs, venetoclax and zanubrutinib, into long-acting nanoformulations (VZ-DCNPs). VZ-DCNPs exhibit synchronized and enhanced cell uptake and plasma exposure of both venetoclax and zanubrutinib. Both drugs are stabilized by lipid excipients to produce the VZ-DcNP nanoparticulate (d ~ 40 nm) product in suspension. The VZ-DcNP formulation has enhanced uptake of the two drugs (VZ) in immortalized leukemic cells (HL-60), threefold over that of its free drug counterpart. Additionally, drug-target selectivity of VZ was noted with MOLT-4 and K562 cells that overexpress each target. When given subcutaneously to mice, the half-lives of venetoclax and zanubrutinib were extended by approximately 43- and 5-fold, respectively, compared to an equivalent free VZ. Collectively, these data suggest that VZ in VZ-DcNP warrant consideration for preclinical and clinical development as a synchronized and long-acting drug-combination for the treatment of leukemia. Full article
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16 pages, 3777 KiB  
Article
Synergistic Pro-Apoptotic Effect of a Cyclic RGD Peptide-Conjugated Magnetic Mesoporous Therapeutic Nanosystem on Hepatocellular Carcinoma HepG2 Cells
by Xuanping Zhao, Chuan Liu, Zichao Wang, Yingyuan Zhao, Xuyang Chen, Haizhen Tao, Hong Chen, Xueqin Wang and Shaofeng Duan
Pharmaceutics 2023, 15(1), 276; https://doi.org/10.3390/pharmaceutics15010276 - 13 Jan 2023
Cited by 5 | Viewed by 2170
Abstract
Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it [...] Read more.
Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGDSPIO@MSN NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the prepared RGDSPIO@MSN NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that the RGDSPIO@MSN@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma. Full article
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Review

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18 pages, 6381 KiB  
Review
Heterocyclic Molecular Targeted Drugs and Nanomedicines for Cancer: Recent Advances and Challenges
by Junxia Liu, Tengfei Chao, Yingying Liu, Chen Gong, Yinan Zhang and Huihua Xiong
Pharmaceutics 2023, 15(6), 1706; https://doi.org/10.3390/pharmaceutics15061706 - 10 Jun 2023
Cited by 2 | Viewed by 1467
Abstract
Cancer is a top global public health concern. At present, molecular targeted therapy has emerged as one of the main therapies for cancer, with high efficacy and safety. The medical world continues to struggle with the development of efficient, extremely selective, and low-toxicity [...] Read more.
Cancer is a top global public health concern. At present, molecular targeted therapy has emerged as one of the main therapies for cancer, with high efficacy and safety. The medical world continues to struggle with the development of efficient, extremely selective, and low-toxicity anticancer medications. Heterocyclic scaffolds based on the molecular structure of tumor therapeutic targets are widely used in anticancer drug design. In addition, a revolution in medicine has been brought on by the quick advancement of nanotechnology. Many nanomedicines have taken targeted cancer therapy to a new level. In this review, we highlight heterocyclic molecular-targeted drugs as well as heterocyclic-associated nanomedicines in cancer. Full article
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31 pages, 2647 KiB  
Review
Drug Delivery Strategies for the Treatment of Pancreatic Cancer
by Oluwabukunmi Olajubutu, Omotola D. Ogundipe, Amusa Adebayo and Simeon K. Adesina
Pharmaceutics 2023, 15(5), 1318; https://doi.org/10.3390/pharmaceutics15051318 - 22 Apr 2023
Cited by 7 | Viewed by 3450
Abstract
Pancreatic cancer is fast becoming a global menace and it is projected to be the second leading cause of cancer-related death by 2030. Pancreatic adenocarcinomas, which develop in the pancreas’ exocrine region, are the predominant type of pancreatic cancer, representing about 95% of [...] Read more.
Pancreatic cancer is fast becoming a global menace and it is projected to be the second leading cause of cancer-related death by 2030. Pancreatic adenocarcinomas, which develop in the pancreas’ exocrine region, are the predominant type of pancreatic cancer, representing about 95% of total pancreatic tumors. The malignancy progresses asymptomatically, making early diagnosis difficult. It is characterized by excessive production of fibrotic stroma known as desmoplasia, which aids tumor growth and metastatic spread by remodeling the extracellular matrix and releasing tumor growth factors. For decades, immense efforts have been harnessed toward developing more effective drug delivery systems for pancreatic cancer treatment leveraging nanotechnology, immunotherapy, drug conjugates, and combinations of these approaches. However, despite the reported preclinical success of these approaches, no substantial progress has been made clinically and the prognosis for pancreatic cancer is worsening. This review provides insights into challenges associated with the delivery of therapeutics for pancreatic cancer treatment and discusses drug delivery strategies to minimize adverse effects associated with current chemotherapy options and to improve the efficiency of drug treatment. Full article
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