Editorial

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3 pages, 156 KiB

Open AccessEditorial

EPR Effect-Based Tumor Targeted Nanomedicine: A Promising Approach for Controlling Cancer

by Jun Fang

J. Pers. Med. 2022, 12(1), 95; https://doi.org/10.3390/jpm12010095 - 12 Jan 2022

Cited by 17 | Viewed by 1778

Abstract

Cancer remains the major threat to human health in most advanced countries in the world [...] Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

Research

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17 pages, 3826 KiB

Open AccessArticle

Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method

by Xin Wu, Yuhki Yokoyama, Hidekazu Takahashi, Shihori Kouda, Hiroyuki Yamamoto, Jiaqi Wang, Yoshihiro Morimoto, Kazumasa Minami, Tsuyoshi Hata, Awad Shamma, Akira Inoue, Masahisa Ohtsuka, Satoshi Shibata, Shogo Kobayashi, Shuji Akai and Hirofumi Yamamoto

J. Pers. Med. 2021, 11(11), 1160; https://doi.org/10.3390/jpm11111160 - 08 Nov 2021

Cited by 6 | Viewed by 2113

Abstract

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To [...] Read more.

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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12 pages, 1807 KiB

Open AccessArticle

Enhanced Anticancer Activity of Nanoformulation of Dasatinib against Triple-Negative Breast Cancer

by Fatemah Bahman, Valeria Pittalà, Mohamed Haider and Khaled Greish

J. Pers. Med. 2021, 11(6), 559; https://doi.org/10.3390/jpm11060559 - 15 Jun 2021

Cited by 16 | Viewed by 3273

Abstract

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC lacks human epidermal growth factor receptor 2 (HER2) amplification, is hormone independent estrogen (ER) and progesterone receptors (PR) negative, and is not [...] Read more.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC lacks human epidermal growth factor receptor 2 (HER2) amplification, is hormone independent estrogen (ER) and progesterone receptors (PR) negative, and is not reactive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment, but in spite of an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases, and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA–dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA–dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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13 pages, 2330 KiB

Open AccessArticle

EPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect

by Waliul Islam, Shintaro Kimura, Rayhanul Islam, Ayaka Harada, Katsuhiko Ono, Jun Fang, Takuro Niidome, Tomohiro Sawa and Hiroshi Maeda

J. Pers. Med. 2021, 11(6), 487; https://doi.org/10.3390/jpm11060487 - 28 May 2021

Cited by 15 | Viewed by 3957

Abstract

For more than three decades, enhanced permeability and retention (EPR)-effect-based nanomedicines have received considerable attention for tumor-selective treatment of solid tumors. However, treatment of advanced cancers remains a huge challenge in clinical situations because of occluded or embolized tumor blood vessels, which lead [...] Read more.

For more than three decades, enhanced permeability and retention (EPR)-effect-based nanomedicines have received considerable attention for tumor-selective treatment of solid tumors. However, treatment of advanced cancers remains a huge challenge in clinical situations because of occluded or embolized tumor blood vessels, which lead to so-called heterogeneity of the EPR effect. We previously developed a method to restore impaired blood flow in blood vessels by using nitric oxide donors and other agents called EPR-effect enhancers. Here, we show that two novel EPR-effect enhancers—isosorbide dinitrate (ISDN, Nitrol^®) and sildenafil citrate—strongly potentiated delivery of three macromolecular drugs to tumors: a complex of poly(styrene-co-maleic acid) (SMA) and cisplatin, named Smaplatin^® (chemotherapy); poly(N-(2-hydroxypropyl)methacrylamide) polymer-conjugated zinc protoporphyrin (photodynamic therapy and imaging); and SMA glucosamine-conjugated boric acid complex (boron neutron capture therapy). We tested these nanodrugs in mice with advanced C26 tumors. When these nanomedicines were administered together with ISDN or sildenafil, tumor delivery and thus positive therapeutic results increased two- to four-fold in tumors with diameters of 15 mm or more. These results confirmed the rationale for using EPR-effect enhancers to restore tumor blood flow. In conclusion, all EPR-effect enhancers tested showed great potential for application in cancer therapy. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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15 pages, 2767 KiB

Open AccessFeature PaperArticle

Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy

by Shanghui Gao, Rayhanul Islam and Jun Fang

J. Pers. Med. 2021, 11(2), 136; https://doi.org/10.3390/jpm11020136 - 17 Feb 2021

Cited by 9 | Viewed by 2527

Abstract

Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an [...] Read more.

Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent ¹O₂ generation under light irradiation because of micelle formation. However, ¹O₂ was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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Review

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32 pages, 4311 KiB

Open AccessReview

A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond

by Yoshitaka Matsumoto, Nobuyoshi Fukumitsu, Hitoshi Ishikawa, Kei Nakai and Hideyuki Sakurai

J. Pers. Med. 2021, 11(8), 825; https://doi.org/10.3390/jpm11080825 - 23 Aug 2021

Cited by 39 | Viewed by 6354

Abstract

In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion [...] Read more.

In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion beam therapy (CIBT), and boron neutron capture therapy (BNCT). PBT and CIBT have been reported to have excellent therapeutic results owing to the physical characteristics of their Bragg peaks. Variable drug therapies, such as chemotherapy, hormone therapy, and immunotherapy, are combined in various treatment strategies, and treatment effects have been improved. BNCT has a high dose concentration for cancer in terms of nuclear reactions with boron. BNCT is a next-generation RT that can achieve cancer cell-selective therapeutic effects, and its effectiveness strongly depends on the selective ¹⁰B accumulation in cancer cells by concomitant boron preparation. Therefore, drug delivery research, including nanoparticles, is highly desirable. In this review, we introduce both clinical and basic aspects of particle beam therapy from the perspective of multidisciplinary treatment, which is expected to expand further in the future. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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8 pages, 240 KiB

Open AccessReview

The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application

by Jun Wu

J. Pers. Med. 2021, 11(8), 771; https://doi.org/10.3390/jpm11080771 - 06 Aug 2021

Cited by 278 | Viewed by 9928

Abstract

Chemotherapy for human solid tumors in clinical practice is far from satisfactory. Despite the discovery and synthesis of hundreds of thousands of anticancer compounds targeting various crucial units in cancer cell proliferation and metabolism, the fundamental problem is the lack of targeting delivery [...] Read more.

Chemotherapy for human solid tumors in clinical practice is far from satisfactory. Despite the discovery and synthesis of hundreds of thousands of anticancer compounds targeting various crucial units in cancer cell proliferation and metabolism, the fundamental problem is the lack of targeting delivery of these compounds selectively into solid tumor tissue to maintain an effective concentration level for a certain length of time for drug-tumor interaction to execute anticancer activities. The enhanced permeability and retention effect (EPR effect) describes a universal pathophysiological phenomenon and mechanism in which macromolecular compounds such as albumin and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate in the tumor vascularized area and thus achieve targeting delivery and retention of anticancer compounds into solid tumor tissue. Targeting therapy via the EPR effect in clinical practice is not always successful since the strength of the EPR effect varies depending on the type and location of tumors, status of blood perfusion in tumors, and the physical-chemical properties of macromolecular anticancer agents. This review highlights the significance of the concept and mechanism of the EPR effect and discusses methods for better utilizing the EPR effect in developing smarter macromolecular nanomedicine to achieve a satisfactory outcome in clinical applications. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

17 pages, 1368 KiB

Open AccessReview

The Potential Role of Sildenafil in Cancer Management through EPR Augmentation

by Mohamed Haider, Amr Elsherbeny, Valeria Pittalà, Antonino N. Fallica, Maha Ali Alghamdi and Khaled Greish

J. Pers. Med. 2021, 11(6), 585; https://doi.org/10.3390/jpm11060585 - 21 Jun 2021

Cited by 17 | Viewed by 6455

Abstract

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for [...] Read more.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the downregulation of Bcl-xL and FAP-1 expression, enhancing reactive oxygen species (ROS) generation, phosphorylating BAD and Bcl-2, upregulating caspase-3,8,9 activities, and blocking cells at G0/G1 cell cycle phase. Sildenafil has also demonstrated inhibitory effects on the efflux activity of ATP-binding cassette (ABC) transporters such as ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing multidrug resistance. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. In this review, we critically examine the basic molecular mechanism of sildenafil related to cancer biology and discuss the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery, pointing to the outcomes of the most important related preclinical and clinical studies. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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27 pages, 1088 KiB

Open AccessFeature PaperReview

Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment

by Md Abdus Subhan, Satya Siva Kishan Yalamarty, Nina Filipczak, Farzana Parveen and Vladimir P. Torchilin

J. Pers. Med. 2021, 11(6), 571; https://doi.org/10.3390/jpm11060571 - 18 Jun 2021

Cited by 207 | Viewed by 8798

Abstract

Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood [...] Read more.

Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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20 pages, 2938 KiB

Open AccessFeature PaperReview

In Situ Delivery and Production System (iDPS) of Anti-Cancer Molecules with Gene-Engineered Bifidobacterium

by Shun’ichiro Taniguchi

J. Pers. Med. 2021, 11(6), 566; https://doi.org/10.3390/jpm11060566 - 17 Jun 2021

Cited by 7 | Viewed by 2638

Abstract

To selectively and continuously produce anti-cancer molecules specifically in malignant tumors, we have established an in situ delivery and production system (iDPS) with Bifidobacterium as a micro-factory of various anti-cancer agents. By focusing on the characteristic hypoxia in cancer tissue for [...] Read more.

To selectively and continuously produce anti-cancer molecules specifically in malignant tumors, we have established an in situ delivery and production system (iDPS) with Bifidobacterium as a micro-factory of various anti-cancer agents. By focusing on the characteristic hypoxia in cancer tissue for a tumor-specific target, we employed a gene-engineered obligate anaerobic and non-pathogenic bacterium, Bifidobacterium, as a tool for systemic drug administration. This review presents and discusses the anti-tumor effects and safety of the iDPS production of numerous anti-cancer molecules and addresses the problems to be improved by directing attention mainly to the hallmark vasculature and so-called enhanced permeability and retention effect of tumors. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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17 pages, 3552 KiB

Open AccessReview

The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

by Hiroshi Maeda

J. Pers. Med. 2021, 11(3), 229; https://doi.org/10.3390/jpm11030229 - 22 Mar 2021

Cited by 87 | Viewed by 5269

Abstract

This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history [...] Read more.

This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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26 pages, 1717 KiB

Open AccessReview

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

by Dong Huang, Lingna Sun, Leaf Huang and Yanzuo Chen

J. Pers. Med. 2021, 11(2), 124; https://doi.org/10.3390/jpm11020124 - 14 Feb 2021

Cited by 65 | Viewed by 5266

Abstract

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, [...] Read more.

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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22 pages, 4766 KiB

Open AccessReview

HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery

by Petr Chytil, Libor Kostka and Tomáš Etrych

J. Pers. Med. 2021, 11(2), 115; https://doi.org/10.3390/jpm11020115 - 10 Feb 2021

Cited by 39 | Viewed by 4585

Abstract

Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight [...] Read more.

Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, antimicrobial molecules, or multidrug resistance inhibitors. Covalent attachment of carried molecules using a biodegradable spacer is strongly preferred, as such design ensures the controlled release of the drug in the place of a desired pharmacological effect in a reasonable time-dependent manner. Importantly, the synthetic polymer biomaterials based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are recognized drug carriers with unique properties that nominate them among the most serious nanomedicines candidates for human clinical trials. This review focuses on advances in the development of HPMA copolymer-based nanomedicines within the passive and active targeting into the place of desired pharmacological effect, tumors, inflammation or bacterial infection sites. Specifically, this review highlights the safety issues of HPMA polymer-based drug carriers concerning the structure of nanomedicines. The main impact consists of the improvement of targeting ability, especially concerning the enhanced and permeability retention (EPR) effect. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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25 pages, 7078 KiB

Open AccessReview

Newly Developed Self-Assembling Antioxidants as Potential Therapeutics for the Cancers

by Babita Shashni and Yukio Nagasaki

J. Pers. Med. 2021, 11(2), 92; https://doi.org/10.3390/jpm11020092 - 02 Feb 2021

Cited by 14 | Viewed by 2353

Abstract

Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) [...] Read more.

Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) antioxidants such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO), although they are catalytically effective in vitro, exerts off-target effects in vivo due to their size, thus, limiting their clinical use. Here, we discuss the superior impacts of our TEMPO radical-conjugated self-assembling antioxidant nanoparticle (RNP) compared to the LMW counterpart in terms of pharmacokinetics, therapeutic effect, and adverse effects in various cancer models. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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19 pages, 1023 KiB

Open AccessFeature PaperReview

Harnessing Extracellular Matrix Biology for Tumor Drug Delivery

by Nithya Subrahmanyam and Hamidreza Ghandehari

J. Pers. Med. 2021, 11(2), 88; https://doi.org/10.3390/jpm11020088 - 31 Jan 2021

Cited by 14 | Viewed by 3752

Abstract

The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the [...] Read more.

The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the ECM holds opportunities for cancer therapy on several fronts. There are targets in the tumor-associated ECM at the level of signaling molecules, enzyme expression, protein structure, receptor interactions, and others. In particular, the ECM is implicated in invasiveness of tumors through its signaling interactions with cells. By capitalizing on the biology of the tumor microenvironment and the opportunities it presents for intervention, the ECM has been investigated as a therapeutic target, to facilitate drug delivery, and as a prognostic or diagnostic marker for tumor progression and therapeutic intervention. This review summarizes the tumor ECM biology as it relates to drug delivery with emphasis on design parameters targeting the ECM. Full article

(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)

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