Targeted Lymphoma Therapy Using a Gold Nanoframework-Based Drug Delivery System

Abstract

Precision nanomedicine can be employed as an alternative to chemo-or radiotherapy to overcome challenges associated with the often narrow therapeutic window of traditional treatment approaches, while safely inducing effective, targeted antitumor responses. Herein, we report the formulation of a therapeutic nanocomposite comprising a hyaluronic acid (HA)coated gold nanoframework (AuNF) delivery system and encapsulated IT848, a small molecule with potent antilymphoma and -myeloma properties that targets the transcriptional activity of nuclear factor kappa B (NF-κB). The porous AuNFs fabricated via a liposome-templated approach were loaded with IT848 and surfacefunctionalized with HA to formulate the nanotherapeutics that were able to efficiently deliver the payload with high specificity to myeloma and lymphoma cell lines in vitro. In vivo studies characterized biodistribution, pharmacokinetics, and safety of HA-AuNFs, and we demonstrated superior efficacy of HA-AuNF-formulated IT848 vs free IT848 in lymphoma mouse models. Both in vitro and in vivo results affirm that the AuNF system can be adopted for targeted cancer therapy, improving the drug safety profile, and enhancing its efficacy with minimal dosing. HA-AuNF-formulated IT848 therefore has strong potential for clinical translation.

The Golden Liposomes: Preparation and Biomedical Applications of Gold-Liposome Nanocomposites

“…AuNP-liposome nanocomposites synthesized with biodegradable lipid accumulate gradually in the liver and are subjected to biological degradation by lipid enzymes resulting in losing the spherical morphology and free AuNP redistributing back to plasma and excreted in urine [122]. On the other hand, AuNPliposome nanocomposites coated with PEG have more stable physiochemical properties and pharmacokinetic profile with enhanced permeability and retention (EPR) effect in tumors [193,204], as the half-life was shown in vivo to reach up to 25 hours, staying in the body for up to 14 days [122].…”

Dual-Targeting Biomimetic Nanomaterials for Photo-/Chemo-/Antiangiogenic Synergistic Therapy

“…Conventional tumor nanomedicine has aroused extensive attention in cancer diagnosis and treatment because of the desirable blood circulation time and prior accumulation at the tumor tissue by enhanced permeability and retention (EPR) effect. 1,2 The rapid development of phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), based on nanotechnology holds tremendous promise because of its noninvasive nature, high selectivity, and negligible systemic cytotoxicity in emerging therapies. 3−6 However, as with other monotherapies, phototherapy itself has inherent drawbacks, in which the partial pressure of oxygen in solid tumors is lower (only 10 mmHg) than in normal peripheral tissues (40−60 mmHg), seriously hampering the effect of oxygen-dependent PDT.…”

“…Conventional tumor nanomedicine has aroused extensive attention in cancer diagnosis and treatment because of the desirable blood circulation time and prior accumulation at the tumor tissue by enhanced permeability and retention (EPR) effect. , The rapid development of phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), based on nanotechnology holds tremendous promise because of its noninvasive nature, high selectivity, and negligible systemic cytotoxicity in emerging therapies. – However, as with other monotherapies, phototherapy itself has inherent drawbacks, in which the partial pressure of oxygen in solid tumors is lower (only 10 mmHg) than in normal peripheral tissues (40–60 mmHg), seriously hampering the effect of oxygen-dependent PDT. , Moreover, PTT tends to induce upregulation of heat shock proteins in tumor tissue, resulting in rapid tumor tolerance and ultimately compromising the treatment effect. , Although the synergistic PDT/PTT could increase PDT efficiency by raising the blood flow rate to improve oxygen supply at the tumor site through hyperthermia and PDT can conversely induce heat-resistant tumor cell death, the undesirable penetration depth of excitation light and low specificity of phototheranostic reagents still hinder the synergistic treatment effect. , …”