beta-particles also contributes to generating further therapeutic effects probably due
to the cross-fire and bystander effects.
It will be advantageous that brachytherapy using radiolabeled NPs of one kind
are conjugated with another, as they are able to target multiple cancer specific
markers. This multifunctionality of radiolabeled NPs enables them to localize more
precisely and to give higher radiation dose than the conventional brachytherapy.
Yook et al. suggested brachytherapy using
177 Lu–AuNP as a local treatment for
locally advanced breast cancer [28, 29]. They designed AuNPs conjugated with
177 Lu and panitumumab targeting epidermal growth factor receptor (EGFR), which
were delivered to breast cancer via local intratumoral injection. This
EGFR-targeting NP (
177 Lu–T–AuNP) was more efficiently bound to
EGFR-positive tumor cells and more cytotoxic in vitro than non-targeting nanoseeds (
177 Lu–NT–AuNP) [28]. However, this superiority of targeting NPs in the
therapeutic efficacy was not reproduced in in vivo experiments. In the comparison
experiment of
177 Lu–T–AuNP and
177 Lu–NT–AuNP in vivo, both different types of
AuNPs arrested tumor growth effectively without causing cytotoxicity to adjacent
normal cells, but they failed to show significant difference in therapeutic efficacy
[29]. This is in the same line with disputes over the superiority (or non-inferiority)
issue of active targeting versus passive targeting (or non-targeting). It is interesting
in that the superiority of targeting strategy was not reproduced in vivo and by
intratumoral injection of radiolabeled NPs. So, many variables would have intervened as confounders.
23.6 Therapeutic Effect of Intrinsic Radioactivity
of Nanoparticles
Nanoparticles can utilize their intrinsic (core) radiotherapeutic properties. In this
regard,
198 Au/
199 Au is one good example. Both isotopes of gold possess intrinsic
radioactive properties that are available for theranostic applications;
198
Au (b
ray = 0.96 meV, c ray = 411 keV) and
199 Au (b ray = 0.46 meV, c
ray = 158 keV). Khan et al. developed
198 Au dendrimer composite nanodevices,
and confirmed therapeutic effects of the
198 Au NPs in the treatment of a mouse
melanoma model by intratumoral injection [30]. The therapeutic effects of
198
Au
NPs via intratumoral injection were also assessed in a mouse prostate cancer model.
Chanda et al. designed
198 Au NPs functionalized with epigallocatechin-gallate
(
198 Au NP–EGCg) specifically targeting the laminin receptors that were overexpressed on prostate cancer cells, and they showed the therapeutic effects of
198
Au
NP–EGCg in a mouse prostate cancer model [31]. Shukla et al. confirmed the
therapeutic effects of
198 Au NP–EGCg in a mouse prostate cancer model, too [32].
In this study, approximately 72% of
198 Au NP–EGCg retained in the tumor after
24 h, and 80% of the tumor volume reduced after 28 days.
23 Therapeutic/Theranostic Use of Radionanomedicine
439
to the cross-fire and bystander effects.
It will be advantageous that brachytherapy using radiolabeled NPs of one kind
are conjugated with another, as they are able to target multiple cancer specific
markers. This multifunctionality of radiolabeled NPs enables them to localize more
precisely and to give higher radiation dose than the conventional brachytherapy.
Yook et al. suggested brachytherapy using
177 Lu–AuNP as a local treatment for
locally advanced breast cancer [28, 29]. They designed AuNPs conjugated with
177 Lu and panitumumab targeting epidermal growth factor receptor (EGFR), which
were delivered to breast cancer via local intratumoral injection. This
EGFR-targeting NP (
177 Lu–T–AuNP) was more efficiently bound to
EGFR-positive tumor cells and more cytotoxic in vitro than non-targeting nanoseeds (
177 Lu–NT–AuNP) [28]. However, this superiority of targeting NPs in the
therapeutic efficacy was not reproduced in in vivo experiments. In the comparison
experiment of
177 Lu–T–AuNP and
177 Lu–NT–AuNP in vivo, both different types of
AuNPs arrested tumor growth effectively without causing cytotoxicity to adjacent
normal cells, but they failed to show significant difference in therapeutic efficacy
[29]. This is in the same line with disputes over the superiority (or non-inferiority)
issue of active targeting versus passive targeting (or non-targeting). It is interesting
in that the superiority of targeting strategy was not reproduced in vivo and by
intratumoral injection of radiolabeled NPs. So, many variables would have intervened as confounders.
23.6 Therapeutic Effect of Intrinsic Radioactivity
of Nanoparticles
Nanoparticles can utilize their intrinsic (core) radiotherapeutic properties. In this
regard,
198 Au/
199 Au is one good example. Both isotopes of gold possess intrinsic
radioactive properties that are available for theranostic applications;
198
Au (b
ray = 0.96 meV, c ray = 411 keV) and
199 Au (b ray = 0.46 meV, c
ray = 158 keV). Khan et al. developed
198 Au dendrimer composite nanodevices,
and confirmed therapeutic effects of the
198 Au NPs in the treatment of a mouse
melanoma model by intratumoral injection [30]. The therapeutic effects of
198
Au
NPs via intratumoral injection were also assessed in a mouse prostate cancer model.
Chanda et al. designed
198 Au NPs functionalized with epigallocatechin-gallate
(
198 Au NP–EGCg) specifically targeting the laminin receptors that were overexpressed on prostate cancer cells, and they showed the therapeutic effects of
198
Au
NP–EGCg in a mouse prostate cancer model [31]. Shukla et al. confirmed the
therapeutic effects of
198 Au NP–EGCg in a mouse prostate cancer model, too [32].
In this study, approximately 72% of
198 Au NP–EGCg retained in the tumor after
24 h, and 80% of the tumor volume reduced after 28 days.
23 Therapeutic/Theranostic Use of Radionanomedicine
439