Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

Habib, Saffiya; Singh, Moganavelli

doi:10.3390/polym14040712

Cited by 29 publications

(19 citation statements)

References 158 publications

(157 reference statements)

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“…Clinical trials have since been conducted for cancer and fungal infections, utilizing liposomes to deliver doxorubicin and amphotericin B [ 37 ]. One of the optimistic outcomes of the application of nanomedicine involves using brain tumor targeting for efficient passage across the BBB [ 8 , 44 ]. The current review will discuss the organic class of NPs and focus on lipid NPs (LNPs).…”

Section: Nanomedicinementioning

confidence: 99%

“…When designing appropriate LNPs for traversing the BBB, the brain itself needs to be prioritized to develop a strategy to bypass the physiological mechanisms in place to prevent the entry of foreign substances. Within the structure of the BBB are brain capillary endothelial cells, pericytes, perivascular mast cells, basement membranes, astrocytes, and neuronal cells, which govern the exchange of molecules between the blood and the brain [ 8 , 33 , 63 , 64 ]. The brain capillary endothelial cells (BCECs) provide a significant protective ability via their close attachment to each other, creating a tight junction.…”

Section: Lnps and The Blood–brain Barriermentioning

confidence: 99%

“…The brain capillary endothelial cells (BCECs) provide a significant protective ability via their close attachment to each other, creating a tight junction. This tight junction eliminates the risk of harmful toxins and pathogens entering the brain, while the degrading enzymes act as a secondary defense mechanism [ 8 , 65 ].…”

Section: Lnps and The Blood–brain Barriermentioning

confidence: 99%

“…Drugs such as levodopa and ropinirole have been met with challenges, especially their need to cross the blood–brain barrier (BBB). Due to the protective ability of the BBB to resist the permeability of foreign molecules into the brain [ 8 ], the drugs that are administered constitute low concentrations of dopamine, which result in several side effects in patients [ 9 , 10 ]. The emergence of nanomedicine with its array of nanoparticles (NPs) has unfolded a new route for therapy.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease

Jagaran

Singh

2022

IJMS

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Parkinson’s disease (PD), a neurodegenerative disorder, is a life-altering, debilitating disease exhibiting a severe physical, psychological, and financial burden on patients. Globally, approximately 7–10 million people are afflicted with this disease, with the number of cases estimated to increase to 12.9 million by 2040. PD is a progressive movement disorder with nonmotor symptoms, including insomnia, depression, anxiety, and anosmia. While current therapeutics are available to PD patients, this treatment remains palliative, necessitating alternative treatment approaches. A major hurdle in treating PD is the protective nature of the blood–brain barrier (BBB) and its ability to limit access to foreign molecules, including therapeutics. Drugs utilized presently are nonspecific and administered at dosages that result in numerous adverse side effects. Nanomedicine has emerged as a potential strategy for treating many diseases. From the array of nanomaterials available, lipid nanoparticles (LNPs) possess various advantages, including enhanced permeability to the brain via passive diffusion and specific and nonspecific transporters. Their bioavailability, nontoxic nature, ability to be conjugated to drugs, and targeting moieties catapult LNPs as a promising therapeutic nanocarriers for PD. While PD-related studies are limited, their potential as therapeutics is evident in their formulations as vaccines. This review is aimed at examining the roles and properties of LNPs that make them efficient therapeutic nanodelivery vehicles for the treatment of PD, including therapeutic advances made to date.

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Section: Nanomedicinementioning

confidence: 99%

Section: Lnps and The Blood–brain Barriermentioning

confidence: 99%

Section: Lnps and The Blood–brain Barriermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease

Jagaran

Singh

2022

IJMS

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“…The amyloid β-protein (APPI), which accumulates in the neuritic plaques and cerebrovascular deposits of patients with Alzheimer’s disease, also contains a Kunitz-domain sequence [ 18 , 19 ]. Angiopeps, a family of KTPI, are used to deliver pharmacological agents to the brain and Angiopep-2-conjugated molecules showed good tolerance in phase I clinical studies and reached phase II for the treatment of recurrent-breast-cancer brain metastasis [ 20 , 21 ]. As natural protease inhibitors, the Kunitz domain is contained in the protein ecallantide that has recently been approved for the treatment of hereditary angioedema [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Kunitz-Type Protease Inhibitors from Blister Beetles (Coleoptera, Meloidae)

et al. 2022

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Protease inhibitors are widely studied since the unrestricted activity of proteases can cause extensive organ lesions. In particular, elastase activity is involved in the pathophysiology of acute lung injury, for example during SARS-CoV-2 infection, while serine proteases and thrombin-like proteases are involved in the development and/or pathology of the nervous system. Natural protease inhibitors have the advantage to be reversible and with few side effects and thus are increasingly considered as new drugs. Kunitz-type protease inhibitors (KTPIs), reported in the venom of various organisms, such as wasps, spiders, scorpions, and snakes, have been studied for their potent anticoagulant activity and widespread protease inhibitor activity. Putative KTPI anticoagulants have been identified in transcriptomic resources obtained for two blister beetle species, Lydus trimaculatus and Mylabris variabilis. The KTPIs of L. trimaculatus and M. variabilis were characterized by combined transcriptomic and bioinformatics methodologies. The full-length mRNA sequences were divided on the base of the sequence of the active sites of the putative proteins. In silico protein structure analyses of each group of translational products show the biochemical features of the active sites and the potential protease targets. Validation of these genes is the first step for considering these molecules as new drugs for use in medicine.

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Metal–Organic Cage as Single‐Molecule Carrier for Solid‐State Nanopore Analysis

Wang

Zhu

et al. 2022

Small Methods

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The ability to detect biomolecules at the single‐molecule level is at the forefront of biological research, precision medicine, and early diagnosis. Recently, solid‐state nanopore sensors have emerged as a promising technique for label‐free and precise diagnosis assay. However, insufficient sensitivity and selectivity for small analytes are a great challenge for clinical diagnosis applications via solid‐state nanopores. Here, for the first time, a metal–organic cage, PCC‐57, is employed as a carrier to increase the sensitivity and selectivity of solid‐state nanopores based on the intrinsic interaction of the nanocage with biomolecules. Firstly, it is found that the carrier itself is undetectable unless bound with the target analytes and used oligonucleotides as linkers to attach PCC‐57 and target analytes. Secondly, two small analytes, oligonucleotide conjugated angiopep‐2 and polyphosphoric acid, are successfully distinguished using the molecular carrier. Finally, selectivity of nanopore detection is achieved by attaching PCC‐57 to oligonucleotide‐tailed aptamers, and the human alpha‐thrombin sample is successfully detected. It is believed that the highly designable metal–organic cage could serve as a rich carrier repository for a variety of biomolecules, facilitating single‐molecule screening of clinically relevant biomolecules based on solid‐state nanopores in the future.

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Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

Cited by 29 publications

References 158 publications

Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease

Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease

Molecular Characterization of Kunitz-Type Protease Inhibitors from Blister Beetles (Coleoptera, Meloidae)

Metal–Organic Cage as Single‐Molecule Carrier for Solid‐State Nanopore Analysis

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