Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model

Abstract

Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.

An analysis on Cancer Nanotherapy: does Nanotechnology have a delivery problem?

“…This study also shows the superiority of the doi: 10.11605/j.pnrs.201802001 hydrogel over the systemic and intra-tumor injections, providing convincing evidence that the local administration using a hydrogel is instrumental to the achievement of superior therapeutic performance [37].…”

“…In fact, a local therapeutic vehicle opens up new vistas for effective neoadjuvant therapy, treat non-resectable tumors, or for washout procedure following tumor resection to prevent recurrence [37].…”

“…In another striking example, Conde et al developed hydrogels optimized as prophylactic patches able to perform gene, chemo and phototherapy in a triple-combination approach to achieve complete tumor resection (more than 90% tumor size reduction) when applied to non-resected tumors and to the absence of tumor recurrence when applied following tumor resection [37]. This study also shows the superiority of the doi: 10.11605/j.pnrs.201802001 hydrogel over the systemic and intra-tumor injections, providing convincing evidence that the local administration using a hydrogel is instrumental to the achievement of superior therapeutic performance [37].…”

Hydrogel-based phototherapy for fighting cancer and bacterial infection

“…Hydrogel-based systems can also be used in combination therapy (Table 2) [48][49][50][51][52][53][54][55][56][57][58][59].…”

Self-Healing Hydrogels as Biomedical Scaffolds for Cell, Gene and Drug Delivery

“…RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs), antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR-Cas9, there is great potential to attack genes and genetic products that are currently untreatable, and to produce a new treatment model in the disease [82][83][84] . Since the first RNA interference report (RNAi) in 1998, there has been great interest in applying RNAi therapy to inhibit histopathological gene expression.…”