Synergistic delivery of gold nanorods using multifunctional microbubbles for enhanced plasmonic photothermal therapy

Abstract

Plasmonic photothermal therapy (PPTT) using plasmonic nanoparticles as efficient photoabsorbing agents has been proposed previously. One critical step in PPTT is to effectively deliver gold nanoparticles into the cells. This study demonstrates that the delivery of gold nanorods (AuNRs) can be greatly enhanced by combining the following three mechanisms: AuNRs encapsulated in protein-shell microbubbles (AuMBs), molecular targeting, and sonoporation employing acoustic cavitation of microbubbles (MBs). Both in vitro and in vivo tests were performed. For molecular targeting, the AuMBs were modified with anti-VEGFR2. Once bound to the angiogenesis markers, the MBs were destroyed by ultrasound to release the AuNRs and the release was confirmed by photoacoustic measurements. Additionally, acoustic cavitation was induced during MB destruction for sonoporation (i.e., increase in transient cellular permeability). The measured inertial cavitation dose was positively correlated with the temperature increase at the tumor site. The quantity of AuNRs delivered into the cells was also determined by measuring the mass spectrometry and observed using third-harmonic-generation microscopy and two-photon fluorescence microscopy. A temperature increase of 20°C was achieved in vitro. The PPTT results in vivo also demonstrated that the temperature increase (>45°C) provided a sufficiently high degree of hyperthermia. Therefore, synergistic delivery of AuNRs was demonstrated.

Direct Permeation of Nanoparticles across Cell Membrane: A Review

“…Meanwhile, an increase in cellular mortality can often be a great concern in these physical methods, if cells are subjected to the excess stress derived from the applied external forces. With regard to the direct delivery of NPs, the electroporation Kawano et al, 2006;Kim et al, 2011;Lin et al, 2009;Zu et al, 2014) and sonoporation (Carrasco et al, 2016;Wang et al, 2014;Yang et al, 2011) have been utilized in recent. In the following, these studies will be reviewed.…”

“…Another approach in which NPs/microbubble composites are synthesized and utilized for better delivery of NPs has also been investigated. Wang et al (2014) synthesized a gold nanorod (AuNR)-microbubble composite, in which AuNRs were encapsulated in perfluorocarbon gas filled microbubbles (3 to 5 μm diameter) covered with a protein/ antibody shell. Amount of the AuNRs delivered into tumor cells showed significant increase when the AuNR/ microbubble composite was used with a sonoporation treatment as compared to the control condition (without encapsulation of AuNRs in microbubbles).…”

“…Operating conditions of the sonoporation treatment (e.g., intensity, frequency, duration of the ultrasound irradiation) can be key factors. Wang et al (2014) and Yang et al (2011) suggested that NP delivery rate can be controlled by the intensity and number of the ultrasound irradiation. Physico-chemical properties of NPs can also be important factors.…”

“…The physical methods were originally developed for gene transfer into cells. Recently, these are exploited for the direct delivery of NPs (Carrasco et al, 2016;Huang et al, 2014;Kawano et al, 2006;Kim et al, 2011;Lin et al, 2009;Wang et al, 2014;Yang et al, 2011;Zu et al, 2014).…”

Progress of nanotechnology for phototherapy: Fundamentals and applications

“…NPs for dual-modality of fluorescence and magnetic resonance imaging-guided, and dual-therapy using photothermal therapy (PTT) and photodynamic therapy (PDT) have been developed recently [11][12][13][14][15][16][17][18][19][20][21][22], where synergic treatment modalities combining PDT with PTT could overcome current limitations of PDT, thus achieving enhanced anticancer efficacy.…”