Nanodiamond‐Based Platform for Intracellular‐Specific Delivery of Therapeutic Peptides against Hepatocellular Carcinoma

Abstract

Therapeutic peptides are attractive as a treatment modality due to their high selectivity and relative safety and tolerability. Delivery of therapeutic peptides to target cells continues to pose a challenge, particularly when these peptides target intracellular proteins. In this study, the use of nanodiamonds (NDs) as a platform for enhanced intracellular delivery of therapeutic peptides is investigated. SALL4 is found to contribute to tumor progression in many types of cancers, including hepatocellular carcinoma (HCC). Therapeutic peptides specifically targeting SALL4 demonstrate an effective, but limited, inhibitory effect on SALL4-driven HCC tumor cell growth. Nanodiamond-based delivery of SALL4-inhibitory peptides is found to improve peptide stability and cellular peptide retention. Stimuli-responsive release of SALL4-inhibitory peptide from nanodiamonds ensures intracellular-specific delivery of functional SALL4-inhibitory peptides. The observed enhanced peptide stability and intracellular-specific delivery of SALL4-inhibitory peptides by nanodiamonds result in improved therapeutic efficacy by ND-peptide complexes against SALL4-driven HCC. As such, nanodiamonds serve as a promising platform for stimuli-responsive intracellular-specific delivery of therapeutic peptides.Therapeutic peptides have been applied toward treating a wide range of diseases. [1][2][3][4][5][6] Various therapeutic applications of peptides include serving as hormones, inhibitors, drug carriers, and even anticancer agents. [1][2][3][4][7][8][9][10][11][12][13] However, hurdles toward clinical implementation for some peptides exist due to the intrinsic

Tailored nanodiamonds for hyperpolarized C13 MRI

“…Finding nanoparticles of biologically-relevant size that combine long T 1 with the ability to create high 13 C polarization has proven to be challenging. With the correct balance of paramagnetic defects to fuel DNP without overly accelerating relaxation, hyperpolarized nanodiamond holds the promise of a biocompatible [22,23] MRI imaging agent possessing the advantages over silicon of optical trackability [24][25][26][27] and a readily-functionalized, non-oxidizing surface [28,29]. Although previous works have investigated 29 Si defects and DNP [30], as well as nitrogen-vacancy defects in diamonds, including recent work hyperpolarizing diamond powders via optical methods [31,32], little has been done to investigate the optimum defect concentration for nanodiamond DNP.…”

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma

“…SOR-NPs have a small diameter and large surface area, which increases the solubility of SOR. Furthermore, the characteristics of SOR-NPs can be controlled to facilitate delivery to the target tumor tissue 39 , 40 . In addition, the zeta potential and other characteristics of NPs can be engineered to improve cellular response.…”

“…Furthermore, by controlling drug release, NPs effectively reduce the therapeutic dose and frequency of administration. NPs reduce the cytotoxicity and degradation rate of chemotherapy drugs 40 . Moreover, many drug-loaded NPs are delivered to tumor tissues in vivo using magnetic fields, and drug release can be triggered by acidic tumor environments.…”

Enhanced penetrative siRNA delivery by a nanodiamond drug delivery platform against hepatocellular carcinoma 3D models

“…49,50 These properties have been leveraged towards the use of NDs as a platform to deliver a wide range of therapeutic and diagnostic reagents, including chemotherapy drugs, [51][52][53][54][55][56][57] peptides, [58][59][60][61] imaging agents [62][63][64] and genetic materials. [65][66][67][68][69][70][71][72] In cancer, ND-drugs have shown enhanced therapeutic efficacy in a wide range of in vitro and in vivo cancer models, including liver cancer, 53,58,73 pancreatic cancer, 55,57 breast cancer 74 and Ewing sarcoma. 75 Polyglycerolfunctionalized nanodiamonds (ND-PG) conjugated with Cy7 and showed preferential accumulation in the tumors rather than the organs when the nanoparticles were systemically administered into tumor-bearing mice.…”