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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Most solid cancers have blood vessels that produce an extensive number of vascular permeability factors. Therefore, most solid tumors show enhanced vascular permeability that will enable a sufficient supply of oxygen and nutrients to the tumor for rapid growth. Angiogenesis results in high vascular density in these types of tumors, which exhibit extravasation and retention of drugs. This enhanced permeability retention (EPR) serves as a basis for anticancer therapy development. This is because the nature of blood vessels in tumors facilitates the transport of drugs into tumor tissues, unlike in normal tissue, in which this EPR effect driven the delivery of macromolecules does not occur. The EPR effect is dependent on the molecular weight of molecules; particles that are larger than 40 kDa seem to have a prolonged circulation time in the body, thus gradually permeating tumors in a selective manner. In addition, the accumulated macromolecules remain in the tumors for a relatively extended time. The EPR effect is also shown to be mediated by several vascular factors, hence modulating these factors seems critical in augmenting the EPR effect and, therefore, the anticancer drug effects [76].
Fertilization and normal embryonic and early fetal development
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Asim Kurjak, Ritsuko K. Pooh, Aida Salihagic-Kadic, Iva Lausin, Lara Spalldi-Barisic
In some species, implantation is invasive (humans) in difference to some where it is noninvasive. Invasive conceptus tends to be smaller at attachment and only a few trophoblast cells are involved in making contact with the maternal endometrium. Within few hours, increased vascular permeability is observed. This is associated with edema and a progressive sprouting and ingrowth of capillaries. The stromal reaction is particularly marked in primates where it is called primary decidualization reaction. The uterine glandular and decidual tissue adjacent to the invading trophoblast of the conceptus is destroyed. It releases primary metabolic substrates: lipids, carbohydrates, nucleic acids, and proteins, which are taken by the growing conceptus. Decidual tissue thus functions like a large yolk reservoir.
Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
William C. Zamboni, Vladimir Torchilin, Anil K. Patri, Jeff Hrkach, Stephen Stern, Robert Lee, Andre Nel, Nicholas J. Panaro, Piotr Grodzinski
In addition to general pharmacokinetic evaluation, assessing tumor distribution and efficacy of oncology nanomedicines in relevant preclinical cancer models is also crucial. One issue unique to nanomedicine tumor distribution in comparison with small molecules is the dependency upon long systemic circulation and vascular permeability for uptake into the interstitial space. Studies have identified nanoparticle properties associated with long circulation, such as PEGylation and small size, which correlate with increased tumor concentration maxima and total exposure (area-under-the-time-concentration curve; Ref. [66]). However, there have been no systematic studies evaluating the clinical relevance of vascular permeabilities found in these animal models. Studies have shown that tumor vascular pore size can be highly variable in animal xenografts, ranging from hundreds of nanometers to microns [67]. As nanomedicine tumor permeability is at least partially dependent upon vascular pore size, it is important that the tumor model vasculature resemble the clinical case [68]. In addition to histologic type, tumor vascular permeability has also been shown to vary depending on site of tumor implantation, with orthotopic brain tumors, for example, having lower permeability than peripherally implanted tumors [69]. This finding would suggest a role for the tumor microenvironment in vascular permeability.
Radiotherapy-induced enrichment of EGF-modified doxorubicin nanoparticles enhances the therapeutic outcome of lung cancer
Published in Drug Delivery, 2022
Jing Wang, Yan Zhang, GuangPeng Zhang, Li Xiang, HaoWen Pang, Kang Xiong, Yun Lu, JianMei Li, Jie Dai, Sheng Lin, ShaoZhi Fu
Nevertheless, the TME limits the antitumor effect of EGF@DOX-NPs alone. Poor angiogenesis reduces blood flow to tumors, which disrupts the intravenous delivery of chemotherapy agents (Qian et al., 2019). Therefore, improving intratumoral blood flow or local vascular permeability is a feasible strategy for enhancing drug delivery to the tumor site. Radiotherapy can enhance the permeability of blood vessels (Barker et al., 2015; Stapleton et al., 2017), and a single dose of 5 Gy radiotherapy can locally burst the tumor vasculature and promote infiltration of macrophages, significantly increasing drug accumulation in the tumor. In this study, we found that radiotherapy significantly dilated blood vessels in tumor tissues and increased the number of TAMs, conducive for drug delivery to these regions when administered intravenously. Furthermore, the beneficial effect of radiation on drug delivery was directly confirmed by higher DOX concentration at the tumor site in irradiated animals. Potiron et al. showed a significant increase in intratumoral drug concentration post-radiotherapy in two tumor models (Potiron et al., 2019). Also, Kunjachan et al. found that local eruption of tumor blood vessels can enhance the accumulation of drugs at the tumor site (Kunjachan et al., 2015).
Subcutaneous catabolism of peptide therapeutics: bioanalytical approaches and ADME considerations
Published in Xenobiotica, 2022
Simone Esposito, Laura Orsatti, Vincenzo Pucci
The ECM plays a major role in peptide absorption, since it controls the content and the movements of the subcutaneous interstitial fluid (SIF) from and to the cardiovascular and the lymphatic systems (Richter et al. 2012). Vascular permeability depends on the presence of a size barrier, which is regulated by the interendothelial junctions of blood and lymph vessels. Blood capillaries have tighter junctions than lymph vessels, therefore they form a more restrictive barrier to macromolecules (Reitsma et al. 2007; Ono et al. 2017). Together, glycocalyx and interendothelial junction act as a molecular sieve towards fluids, small molecules and proteins that are filtered from blood through capillary walls towards the SIF, and then are either reabsorbed back into the capillaries or taken up by the lymphatic system (Fogh-Andersen et al. 1995; Richter et al. 2012; Moore and Bertram 2018; Torres-Terán et al. 2021). A correlation between the molecular weight of macromolecules and their lymphatic uptake was first proposed by Supersaxo et al. (Supersaxo et al. 1990). Drug peptides SC administered can reach the systemic circulation by blood capillaries or lymphatic vessels uptake. Proteins with high MW (>16kDa) have limited transport into the blood capillaries and are taken up by lymphatic capillaries and lymph nodes and enter the blood circulation through the thoracic duct (Porter and Charman 2000; Kagan 2014).
State-of-the-art of ultrasound-triggered drug delivery from ultrasound-responsive drug carriers
Published in Expert Opinion on Drug Delivery, 2022
Ching-Hsiang Fan, Yi-Ju Ho, Chia-Wei Lin, Nan Wu, Pei-Hua Chiang, Chih-Kuang Yeh
In the tumor microenvironment, the abnormal vessel structure allows nano-sized particles (380–780 nm) to pass through the gap-junctions between vascular endothelial cells and then accumulate in the tumor tissue, termed as enhanced permeability and retention (EPR) effect [47,48]. The passive extravasation of drug-loaded US-responsive NPs from vessels into interstitial tissue after IV injection is also a kind of extravascular drug delivery. Under US stimulation, the mechanical effects induced by intratumoral US-responsive NP cavitation lead to local release of drugs and directly affect cells in the tumor tissues while avoiding intravascular damage [49,50]. The efficiency of the EPR effect is correlated with tumor perfusion, vascular pore size, interstitial fluid pressure, and NP size [51]. To improve NP accumulation, many studies have designed NPs that target tumors and modulate the tumor microenvironment to enhance blood perfusion and decrease interstitial fluid pressure [52,53]. Moreover, US-triggered intravascular delivery also enlarges the vascular pore size (thus enhancing vascular permeability) to increase NP accumulation for subsequent extravascular drug delivery. Nevertheless, as this US-triggered extravascular drug delivery occurs after IV injection, the circulating NPs may still induce some systemic toxicity due to passive extravasation.