Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood–brain barrier divide

Chacko, Ann‐Marie; Li, Chunsheng; Pryma, Daniel A.; Brem, Steven; Coukos, George; Muzykantov, Vladimir R.

doi:10.1517/17425247.2013.808184

Cited by 92 publications

(65 citation statements)

References 135 publications

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“…Recent innovations in radiation therapy have improved precision, tumor definition with imaging, and radiation delivery through beam shaping. 24 In addition to its current utility, radiation therapy may play a role in selectively disrupting the BBB. Studies in both animals and humans have demonstrated that radiation therapy can induce focal BBB disruption with minimal effects on normal vasculature.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Therapeutic strategies to improve drug delivery across the blood-brain barrier

Azad¹,

Pan²,

Connolly³

et al. 2015

FOC

106

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Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

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Section: Therapeutic Implicationsmentioning

confidence: 99%

Therapeutic strategies to improve drug delivery across the blood-brain barrier

Azad¹,

Pan²,

Connolly³

et al. 2015

FOC

106

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show abstract

“…Two notable examples include bradykinin analog RMP-7 and calcium-dependent potassium channels (KCa) [48]. RMP-7 is a bradykinin B2 receptor agonist with an increased half-life over bradykinin.…”

Section: Strategies For Cns Deliverymentioning

confidence: 99%

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Tosi

Marnell

Chang

et al. 2017

IJMS

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Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

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“…Tumor and brain tissue uptake limited by BBB [72]. Cationic Polymers EPR effect and/or targeting group (i.e., cationic moiety) [73].…”

Section: Antibody-dendrimer Conjugatesmentioning

confidence: 99%

“…The advantages of boron-mAb conjugates are their high T/N selectivity and T/B ratios. However, one limitation is that systemic administration of mAbs will result in poor brain tumor uptake due to their limited ability to cross the BBB [72].…”

Section: Antibody-dendrimer Conjugatesmentioning

confidence: 99%

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

2015

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Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

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Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood–brain barrier divide

Cited by 92 publications

References 135 publications

Therapeutic strategies to improve drug delivery across the blood-brain barrier

Therapeutic strategies to improve drug delivery across the blood-brain barrier

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

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