Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells.
07 Dec 2020-Artificial Cells Nanomedicine and Biotechnology (Artif Cells Nanomed Biotechnol)-Vol. 48, Iss: 1, pp 1362-1371
TL;DR: Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death.
Abstract: Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents ang...
Citations
More filters
01 Jun 2021
TL;DR: The present review highlights the phytochemical based nanoformulations in improving the therapeutic response and several alternative ways to target resistance cancer.
Abstract: The graph of drug resistance in cancer is reportedly increasing in terms of therapeutic efficiency. As per the WHO reports, around 70% of death reported in low- and middle-income countries. The increase in death toll was imparted from improper diagnosis and inadequate therapy. The 25% increase in disease burden may be laden due to resistance mutations in cancer during treatment. Exposure of high concentrations of chemotherapeutic agents leads to toxicity in the normal cells. Long-term conventional chemotherapy develops acquired resistance. The conventional therapeutics was not able to target the cancer cell specifically and need to promulgate the use of nanocarrier or bioengineering for the polychemotherapy. Phytochemicals are natural constituents providing alternative therapeutic approach to minimize the resistance. The present review highlights the nano-therapeutic approaches pondering over the conventional chemotherapy. The phytochemicals are extracted, isolated, and purified from daily dietary fibers or natural plants. Natural extractives act via multiple pathways and provide optimum effectiveness against resistance cancer. The poor solubility and bioavailability are major constraints in combination therapy. The nanotechnological approach improves the functional properties transportation across cell barriers, and improves bioavailability. The present review highlights the phytochemical based nanoformulations in improving the therapeutic response and several alternative ways to target resistance cancer. The major implications of phytochemical and chemotherapeutic combination therapy could lead in the future.
30 citations
TL;DR: In this paper , RSV-loaded PLGA nanoparticles were conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models.
Abstract: Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. The specific molecular mechanisms through which PD-associated neuronal loss occurs remain unclear, and there is no available effective treatment against PD-related neurodegeneration. Resveratrol (RSV) has exhibited promising neuroprotective effects via antioxidant and anti-inflammatory activity. However, its poor bioavailability in the brain represents a challenge for its application in PD treatment. In this study, we synthesized RSV-loaded PLGA nanoparticles (RSV-PLGA-NPs) conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models. The Lf-conjugated RSV-PLGA-NPs (Lf-RSV-PLGA-NPs) exhibited enhanced internalization into SH-SY5Y and human brain microvascular endothelial cells as compared to RSV-PLGA-NPs and free RSV. Further, Lf-RSV-PLGA-NPs were more effective than RSV-PLGA-NPs and free RSV in attenuating the MPP+-induced generation of reactive oxygen species, reduction of mitochondrial membrane potential, and cell death. Importantly, Lf conjugation specifically increased the accumulation of RSV-PLGA-NPs in the brain as determined via bioluminescent imaging analyses. Our formulation substantially enhanced the neuroprotective effects of RSV in the MPTP-induced PD model. Hence, Lf-RSV-PLGA-NPs represent a promising tool for improving RSV bioavailability and neuroprotection within the brain.
14 citations
TL;DR: In this paper, the authors demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids, characterized by six-and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom.
Abstract: The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.
13 citations
TL;DR: In this article, a hydrogen peroxide (H2O2) activatable iodinated resorufin (RR-1) was introduced as a red-shifted, water soluble and cancer cell selective photosensitizer, which exhibited high singlet oxygen quantum yield in aqueous solutions upon reacting with H2O 2 and induced selective photocytotoxicity in colorectal (HCT-116) and triple negative breast (MDA MB-231) cancer cells.
Abstract: Enhanced selectivity towards cancer cells is one of the most essential features sought in new generation photodynamic therapy (PDT) agents in order to minimize the side effects on healthy cells and to improve the efficacy of the treatment. In this direction, one promising approach is to design activatable photosensitizers, which tend to stay in an OFF state and get activated only in cancer cells with tumor-associated stimuli. Based on this idea, herein we introduced a hydrogen peroxide (H2O2) activatable iodinated resorufin (RR-1) as a red-shifted, water soluble and cancer cell selective photosensitizer. RR-1 exhibited high singlet oxygen quantum yield in aqueous solutions upon reacting with H2O2 and induced selective photocytotoxicity in colorectal (HCT-116) and triple negative breast (MDA MB-231) cancer cells, which contain high level of reactive oxygen species (ROS). Additionally, fluorescence signal of the iodo-resorufin core was restored upon cleavage of the cage unit in these cancer cells. In contrast, very low photocytotoxicity and negligible fluorescence enhancement were observed in normal fibroblast (NIH-3T3) cells. RR-1 not only marks the first example of a H2O2 activatable resorufin-based photosensitizer but also represents the first ever resorufin-based theranostic agent. We anticipate that iodo-resorufin scaffold can be easily modified with different masking units towards realization of highly selective and efficient phototheranostic agents for treatment of various cancer cells.
9 citations
TL;DR: The current review delineates the mechanistic framework of BA-mediated cancer suppression through the modulation of multiple signaling pathways and also summarizes the key outcomes of BA in preclinical investigations.
Abstract: Natural products serve as the single most productive source for the discovery of drugs and pharmaceutical leads. Among the various chemicals derived from microbes, plants, and animals, phytochemicals have emerged as potential candidates for the development of anticancer drugs due to their structural diversities, complexities, and pleiotropic effects. Herein, we discuss betulinic acid (BA), a ubiquitously distributed lupane structured pentacyclic triterpenoid, scrutinized as a promising natural agent for the prevention, suppression, and management of various human malignancies. Ease of availability, common occurrences, cell‐specific cytotoxicity, and astonishing selectivity are the important factors that contribute to the development of BA as an anticancer agent. The current review delineates the mechanistic framework of BA‐mediated cancer suppression through the modulation of multiple signaling pathways and also summarizes the key outcomes of BA in preclinical investigations.
7 citations
References
More filters
TL;DR: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation and is used to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
Abstract: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
50,114 citations
TL;DR: The basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor.
Abstract: Most solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues or organs, such as extensive angiogenesis and hence hypervasculature, defective vascular architecture, impaired lymphatic drainage/recovery system, and greatly increased production of a number of permeability mediators. The phenomenon now known as the enhanced permeability and retention (EPR) effect for lipid and macromolecular agents has been observed to be universal in solid tumors. Primarily, enhanced vascular permeability will sustain an adequate supply of nutrients and oxygen for rapid tumor growth. The EPR effect also provides a great opportunity for more selective targeting of lipid- or polymer-conjugated anticancer drugs, such as SMANCS and PK-1, to the tumor. In the present review, the basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor. Tumor-specific vascular physiology is also described.
5,955 citations
"Lactoferrin-tethered betulinic acid..." refers background in this paper
...Cellspecific delivery was achieved based on passive enhanced permeability and retention (EPR) effects [3]....
[...]
TL;DR: In this article, the role of dynamic swelling and the dissolution of the polymer matrix on the release mechanism was discussed, as well as the effect of the tracer/excipient ratio on the poly(vinyl alcohol) release profile.
Abstract: Porous hydrophilic discs were prepared from two grades of poly(vinyl alcohol) of varying degree of hydrolysis. The influence of the molecular size of the tracer used (potassium chloride, phenylpropanolamine hydrochloride and bovine serum albumin), that of the addition of a second water-soluble polymer poly(N-vinyl-2-pyrrolidone) and poly(ethylene glycol)) and the effect of the tracer/excipient ratio on the release profile were examined. Finally the role of the dynamic swelling and the dissolution of the polymer matrix on the release mechanism are discussed.
4,397 citations
TL;DR: The in vivo fate of these systems, after intravascular or tumoral administration, is discussed, as well as the mechanism involved in tumor regression, and the application of nanoparticles in imaging for cancer diagnosis is focused on.
Abstract: Numerous investigations have shown that both tissue and cell distribution profiles of anticancer drugs can be controlled by their entrapment in submicronic colloidal systems (nanoparticles). The rationale behind this approach is to increase antitumor efficacy, while reducing systemic side-effects. This review provides an update of tumor targeting with conventional or long-circulating nanoparticles. The in vivo fate of these systems, after intravascular or tumoral administration, is discussed, as well as the mechanism involved in tumor regression. Nanoparticles are also of benefit for the selective delivery of oligonucleotides to tumor cells. Moreover, certain types of nanoparticles showed some interesting capacity to reverse MDR resistance, which is a major problem in chemotherapy. The first experiments, aiming to decorate nanoparticles with molecular ligand for 'active' targeting of cancerous cells, are also discussed here. The last part of this review focus on the application of nanoparticles in imaging for cancer diagnosis.
3,164 citations
"Lactoferrin-tethered betulinic acid..." refers background in this paper
...Nanoparticles are considered as useful weapons in cancer chemotherapy and diagnosis [1,2]....
[...]
TL;DR: In this critical review, insights are provided into the design and development of targeted polymeric NPs and the challenges associated with the engineering of this novel class of therapeutics are highlighted, including considerations of NP design optimization, development and biophysicochemical properties.
Abstract: Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).
1,407 citations
Additional excerpts
...experimented already for active cancer targeting [5]....
[...]